Strengths and considerations
No source-reviewed explanatory claims are recorded here yet.
benchmark · protocol
Missense variants splicing-based classification (AlphaGenome paper)
Can splicing-effect predictions distinguish pathogenic from benign variants in this consequence category?
AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2At a glance
Explanatory profile: limited source coverage · Automated source review, 2026-09-17. Review applies to the cited claims; unresolved fields are listed below. Numerical results retain their own review status.
| Property | Description and evidence |
|---|---|
| Dataset and biological context | ClinVar GRCh38 release 2025-03-23. ClinVar autosomal missense variants with at least one review star, labelled pathogenic/likely pathogenic versus benign/likely benign, restricted to AlphaMissense likely-benign calls.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 |
| Split | Zero-shot scorer development uses validation chromosomes 1,2,4,5,7,8,10,11,13,14,15,17,20,22,X; final test chromosomes are 3,6,9,12,16,18,19,21. This partitions variant evaluation labels; the distilled model’s teachers were trained on all reference-genome folds.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 |
| Allowed inputs and adaptation | REF/ALT sequence, gene annotations and composite splice-site/site-usage/junction scores; the table uses maximum absolute track aggregation.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 |
| Metrics as reported | auprc_max_abs_track_aggregationAlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 |
| Aggregation | auPRC in the category, retaining its own class prevalence and sampling scheme.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 |
| Uncertainty | Not reported for these summary-table scores. · Not reported in inspected sourcesAlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 |
| Entity type | protocol |
| Organisms | Not extracted or verified for this record. |
| Assays | Not extracted or verified for this record. |
| Baselines | Not extracted or verified for this record. |
How it works
Conceptual summary of the cited procedure; model-specific conditions are given below.
Read the diagram as text
- Select labelled ClinVar category
- Apply held-out chromosome split
- Compute composite splicing score
- Evaluate category auPRC
What is tested
Can splicing-effect predictions distinguish pathogenic from benign variants in this consequence category?
AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2Procedure
Score each variant from its predicted splicing changes and compare with the selected ClinVar pathogenicity labels.
AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2Tested models and results
Release 2026-09-17-a757f4af4277 · 2 evaluations · 2 metric rows. Different protocols are not a single leaderboard.
| Metric and finding | Coverage and uncertainty | Evidence |
|---|---|---|
| DeltaSplice (paper Table 4): Missense variants splicing-based classification Model: DeltaSplice (paper Table 4) · Benchmark: Missense variants splicing-based classification (AlphaGenome paper) · Dataset: Missense variants splicing-based classification: evaluated data subset Score each variant from its predicted splicing changes and compare with the selected ClinVar pathogenicity labels. Author-reported evaluation · Evaluation metadata: needs review | ||
| 0.163413 auprc_max_abs_track_aggregation Unit: dimensionless · Direction: higher Aggregation: auPRC in the category, retaining its own class prevalence and sampling scheme. | Uncertainty: unreported Scored: Not reported · Eligible: Not reported | source checkedAlphaGenome Nature 2026 supplementary comparison tables · 'Suppl Table 4 Variant performan'!L2 Source checking is not independent reproduction. |
| AlphaGenome distilled all-fold student: Missense variants splicing-based classification Model: AlphaGenome distilled all-fold student · Benchmark: Missense variants splicing-based classification (AlphaGenome paper) · Dataset: Missense variants splicing-based classification: evaluated data subset Score each variant from its predicted splicing changes and compare with the selected ClinVar pathogenicity labels. Author-reported evaluation · Evaluation metadata: needs review | ||
| 0.18 auprc_max_abs_track_aggregation Unit: dimensionless · Direction: higher Aggregation: auPRC in the category, retaining its own class prevalence and sampling scheme. | Uncertainty: unreported Scored: Not reported · Eligible: Not reported | source checkedAlphaGenome Nature 2026 supplementary comparison tables · 'Suppl Table 4 Variant performan'!M2 Source checking is not independent reproduction. |
Strengths and limitations
Limitations and conditions
- ClinVar pathogenicity is not an experimentally isolated splicing label. Boundary text differs in strict/inclusive wording between methods and Fig3h; use the released category labels rather than inventing edge-case membership.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2
- This is an author-reported protocol, not a rewire rerun. Different datasets, processing and adaptations cannot support an unrestricted leaderboard.AlphaGenome Nature 2026 supplementary comparison tables; AlphaGenome Nature 2026 supplementary methods; alphagenome: Journal full-text XML · 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2
Profile review details
Primary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction.
Stable record: alphagenome-2026-t4-protocol-1Evidence table
Trace each statement to its source and review. A context-only reference supports the record generally; it does not verify an individual field. Source checking does not reproduce an experiment.
One row per statement and cited source. Multiple citations are not independent evaluations. Shared locators are labelled explicitly.
42 evidence rows matching the loaded filters
| Property and statement | Original source and location | Review and provenance |
|---|---|---|
| Diagram caption Conceptual summary of the cited procedure; model-specific conditions are given below. Individual claims | alphagenome: Journal full-text XML 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Retrieved page snapshot; no immutable publisher revision supplied | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of retrieved original artifact bytes Format: original_artifact |
| Diagram caption Conceptual summary of the cited procedure; model-specific conditions are given below. Individual claims | AlphaGenome Nature 2026 supplementary methods 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Supplement to Nature version of record, 28 January 2026; content hash pinned | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of exact publisher PDF bytes Format: original_pdf |
| Diagram caption Conceptual summary of the cited procedure; model-specific conditions are given below. Individual claims | AlphaGenome Nature 2026 supplementary comparison tables 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Nature version of record, 28 January 2026 | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of exact retrieved original artifact bytes Format: xlsx |
| Diagram steps ["Select labelled ClinVar category","Apply held-out chromosome split","Compute composite splicing score","Evaluate category auPRC"] Individual claims | alphagenome: Journal full-text XML 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Retrieved page snapshot; no immutable publisher revision supplied | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of retrieved original artifact bytes Format: original_artifact |
| Diagram steps ["Select labelled ClinVar category","Apply held-out chromosome split","Compute composite splicing score","Evaluate category auPRC"] Individual claims | AlphaGenome Nature 2026 supplementary methods 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Supplement to Nature version of record, 28 January 2026; content hash pinned | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of exact publisher PDF bytes Format: original_pdf |
| Diagram steps ["Select labelled ClinVar category","Apply held-out chromosome split","Compute composite splicing score","Evaluate category auPRC"] Individual claims | AlphaGenome Nature 2026 supplementary comparison tables 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Nature version of record, 28 January 2026 | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of exact retrieved original artifact bytes Format: xlsx |
| Diagram title Missense variants splicing-based classification: evaluation procedure Individual claims | alphagenome: Journal full-text XML 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Retrieved page snapshot; no immutable publisher revision supplied | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of retrieved original artifact bytes Format: original_artifact |
| Diagram title Missense variants splicing-based classification: evaluation procedure Individual claims | AlphaGenome Nature 2026 supplementary methods 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Supplement to Nature version of record, 28 January 2026; content hash pinned | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of exact publisher PDF bytes Format: original_pdf |
| Diagram title Missense variants splicing-based classification: evaluation procedure Individual claims | AlphaGenome Nature 2026 supplementary comparison tables 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Nature version of record, 28 January 2026 | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of exact retrieved original artifact bytes Format: xlsx |
| Dataset and biological context ClinVar GRCh38 release 2025-03-23. ClinVar autosomal missense variants with at least one review star, labelled pathogenic/likely pathogenic versus benign/likely benign, restricted to AlphaMissense likely-benign calls. Individual claims | alphagenome: Journal full-text XML 'Suppl Table 4 Variant performan'!A2:P2; Supplementary Methods p.30, Chromosome Splits for Variant Benchmarks; Supplementary Methods pp.30–31, ClinVar Variants; methods: pp.30–31, ClinVar Variants; paper: Fig.3h; methods: p.30, Chromosome Splits for Variant Benchmarks; paper: Fig.1e; tables: Suppl Table 4 Variant performan; evaluation index 1; sheet rows 2 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Retrieved page snapshot; no immutable publisher revision supplied | source checked automated source review · 2026-09-17 Audit detailsPrimary-source transcription and separate automated source review. No human sign-off or independent experimental reproduction. Field: Source artifact SHA-256: Hash scope: SHA-256 of retrieved original artifact bytes Format: original_artifact |
Sources and history
Release 2026-09-17-a757f4af4277 · Record review: needs review
- AlphaGenome Nature 2026 supplementary comparison tables · Original source · Nature version of record, 28 January 2026
- AlphaGenome Nature 2026 supplementary methods · Original source · Supplement to Nature version of record, 28 January 2026; content hash pinned
- alphagenome: Journal full-text XML · Original source · Retrieved page snapshot; no immutable publisher revision supplied
Technical metadata and extraction receipts
Stable ID: alphagenome-2026-t4-protocol-1
- areas
- dna-genomes
- entity level
- protocol
- version
- Nature version of record, 28 January 2026
- source evaluation index
- 1
- source table
- 4
- reference levels
- metric: auprc_max_abs_track_aggregation; printed value: 0.04781; numeric value: 4.7809999999999998E-2; source locator: Suppl Table 4 Variant performan!J2; note: Source reference quantity for relative-performance calculation, not a measured baseline run.