rewirebio.iobenchmarks
Evidence claim

Relevance of vep-lit-20261014-protocol-livesey2025-clinical-auroc to use-case-missense-pp3-bp4-calibrated-evidence

Use case
Use calibrated computational evidence for missense variants (PP3/BP4)
Assessed by
Livesey and Marsh 2025 clinical benchmark: pairwise AUROC win rate, ClinVar pathogenic versus gnomAD missense
Relevance
Proxy evidence
Endpoint
Average pairwise win rate by per-protein AUROC separating ClinVar P/LP from gnomAD v4.1 missense variants in 819 proteins

Relevance judgement drafted by the extraction agent; independently reviewed, automated review only.

85 reviewed evaluations

Evidence

Source checking verifies the cited claim or transcription. It does not establish independent reproduction.

Evidence table

Inspect claims, sources and review details

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.

19 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-10-22-1b7cf027e4f6
Property and statementOriginal source and locationReview and provenance
Citation locations
1 values
  • source id
    vep-lit-20261014-source-livesey2025-supplementary-2
    locator
    Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.citation_locators

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Comparison group
livesey-marsh-2025-vep-ranking
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.comparison_group

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Comparison title
Livesey and Marsh 2025 VEP rankings
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.comparison_title

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Constraints
3 values
  • Inspect every linked evaluation's source locator before citing a result.
  • Do not combine this mapping's evaluations with any other protocol's results.
  • Compare rows only within this protocol.
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.constraints

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Endpoint
Average pairwise win rate by per-protein AUROC separating ClinVar P/LP from gnomAD v4.1 missense variants in 819 proteins
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.endpoint

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Claimed field
links:assessed_by:vep-lit-20261014-protocol-livesey2025-clinical-auroc
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.field

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Headline metric
pairwise-win-rate
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.headline_metric

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Limitations
6 values
  • No calibration to ACMG/AMP evidence strength and no thresholds.
  • The negative class is gnomAD v4.1 missense variants not classed pathogenic ('putatively benign'); the authors note it will include unclassified pathogenic variants, particularly in recessive and incomplete-penetrance genes (Results).
  • VEPs that use allele frequency as a feature likely benefit from circularity, because frequency is used to classify variants as benign (Discussion); the gnomAD negative class reduces but does not remove this.
  • No training variants were removed; the authors attribute most of the clinical-trained VEPs' advantage over the DMS ranking to circularity (Results, Fig. 4).
  • AUROC is computed per protein, so the ranking does not test whether scores are comparable across genes, which genome-wide thresholds assume.
  • Transcribed from the source; no reproduction by Rewire and no human scientific review.
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.limitations

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

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Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.pins

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

Rationale
Proxy: ranks many more predictors than are calibrated, which helps choose candidates for calibration, but it measures discrimination within proteins, not evidence strength at a threshold.
Context-only references
Livesey and Marsh 2025, Supplementary Material 2 (Tables S1-S8)

Original source ↗

vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'

Version: 13059_2025_3575_MOESM2_ESM.xlsx as published with PMC12016141
Retrieved: 2026-10-14T13:36:25Z

not individually reviewed

No individual claim review recorded

Audit details

Field: attributes.rationale

Source artifact SHA-256: 1b0d792d1a5d3daa95545a7973cabb131c45e42c952e7e5a447a72deef1d1e70

Hash scope: Hash scope not separately documented; inspect source record

How to read the evidence

Sources and history

Release 2026-10-22-1b7cf027e4f6 · Record review: source checked

1 source record and release historyDownload this release (gzip)
Technical metadata and extraction receipts

Stable ID: use-case-mapping-vep-uc-20261014-missense-pp3-bp4-calibrated-evidence-livesey2025-clinical-auroc

field
links:assessed_by:vep-lit-20261014-protocol-livesey2025-clinical-auroc
value
vep-lit-20261014-protocol-livesey2025-clinical-auroc
relevance
proxy
endpoint
Average pairwise win rate by per-protein AUROC separating ClinVar P/LP from gnomAD v4.1 missense variants in 819 proteins
rationale
Proxy: ranks many more predictors than are calibrated, which helps choose candidates for calibration, but it measures discrimination within proteins, not evidence strength at a threshold.
constraints
Inspect every linked evaluation's source locator before citing a result.; Do not combine this mapping's evaluations with any other protocol's results.; Compare rows only within this protocol.
limitations
No calibration to ACMG/AMP evidence strength and no thresholds.; The negative class is gnomAD v4.1 missense variants not classed pathogenic ('putatively benign'); the authors note it will include unclassified pathogenic variants, particularly in recessive and incomplete-penetrance genes (Results).; VEPs that use allele frequency as a feature likely benefit from circularity, because frequency is used to classify variants as benign (Discussion); the gnomAD negative class reduces but does not remove this.; No training variants were removed; the authors attribute most of the clinical-trained VEPs' advantage over the DMS ranking to circularity (Results, Fig. 4).; AUROC is computed per protein, so the ranking does not test whether scores are comparable across genes, which genome-wide thresholds assume.; Transcribed from the source; no reproduction by Rewire and no human scientific review.
citation locators
source id: vep-lit-20261014-source-livesey2025-supplementary-2; locator: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'
source locator
vep-lit-20261014-source-livesey2025-supplementary-2: Supplementary Material 2 Table S8; Methods 'ClinVar and gnomAD data', 'AUROC and AUPRC'
headline metric
pairwise-win-rate
comparison group
livesey-marsh-2025-vep-ranking
comparison title
Livesey and Marsh 2025 VEP rankings
stratum label
Clinical benchmark, ClinVar P/LP versus gnomAD missense
stratum order
6
reason
VEP use-case pass 2026-10-14: relevance of a protocol to a new use case (rewire-benchmark-data #151/#152).
review
reviewer: claude; reviewer note: Claude review agent; no human review claimed. Independent Claude (Opus 5.5) review agent, separate from the extraction agent that built this batch. Automated review only. Transcription, not reproduction.; reviewed at: 2026-10-14T16:00:00Z; method: ai-assisted-source-review; scope-review; method note: Checked the endpoint against the use case's question, inputs, exclusions and output; checked each limitation and number against the cited sources, re-downloaded and hash-matched; listed every evaluation on the protocol in reviewed_evaluations (values of evaluations already in the store were checked by their own independent reviews).; note: Judgement drafted by the extraction agent and revised in review (docs/reviews/vep-use-cases-2026-10-14-review.md).
reviewed evaluations
vep-lit-20261014-eval-livesey2025-clinical-auroc-3cnet; vep-lit-20261014-eval-livesey2025-clinical-auroc-alphamissense; vep-lit-20261014-eval-livesey2025-clinical-auroc-alphscore; vep-lit-20261014-eval-livesey2025-clinical-auroc-bayesdel; vep-lit-20261014-eval-livesey2025-clinical-auroc-bayesdel-noaf; vep-lit-20261014-eval-livesey2025-clinical-auroc-blosum62; vep-lit-20261014-eval-livesey2025-clinical-auroc-cadd-1-7; vep-lit-20261014-eval-livesey2025-clinical-auroc-cadd-unversioned; vep-lit-20261014-eval-livesey2025-clinical-auroc-capice; vep-lit-20261014-eval-livesey2025-clinical-auroc-clinpred; vep-lit-20261014-eval-livesey2025-clinical-auroc-condel; vep-lit-20261014-eval-livesey2025-clinical-auroc-cosmis; vep-lit-20261014-eval-livesey2025-clinical-auroc-cpt-1; vep-lit-20261014-eval-livesey2025-clinical-auroc-dann; vep-lit-20261014-eval-livesey2025-clinical-auroc-deepsav; vep-lit-20261014-eval-livesey2025-clinical-auroc-deepsequence; vep-lit-20261014-eval-livesey2025-clinical-auroc-demask; vep-lit-20261014-eval-livesey2025-clinical-auroc-deogen2; vep-lit-20261014-eval-livesey2025-clinical-auroc-eigen; vep-lit-20261014-eval-livesey2025-clinical-auroc-envision; vep-lit-20261014-eval-livesey2025-clinical-auroc-escott; vep-lit-20261014-eval-livesey2025-clinical-auroc-esm-1b; vep-lit-20261014-eval-livesey2025-clinical-auroc-esm-1v; vep-lit-20261014-eval-livesey2025-clinical-auroc-esm2; vep-lit-20261014-eval-livesey2025-clinical-auroc-eve; vep-lit-20261014-eval-livesey2025-clinical-auroc-evmutation-epistatic; vep-lit-20261014-eval-livesey2025-clinical-auroc-evmutation-independent; vep-lit-20261014-eval-livesey2025-clinical-auroc-fathmm; vep-lit-20261014-eval-livesey2025-clinical-auroc-fathmm-mkl; vep-lit-20261014-eval-livesey2025-clinical-auroc-fathmm-xf; vep-lit-20261014-eval-livesey2025-clinical-auroc-fitcons; vep-lit-20261014-eval-livesey2025-clinical-auroc-gemme; vep-lit-20261014-eval-livesey2025-clinical-auroc-genocanyon; vep-lit-20261014-eval-livesey2025-clinical-auroc-gerp-plus-plus; vep-lit-20261014-eval-livesey2025-clinical-auroc-gmvp; vep-lit-20261014-eval-livesey2025-clinical-auroc-grantham; vep-lit-20261014-eval-livesey2025-clinical-auroc-igemme; vep-lit-20261014-eval-livesey2025-clinical-auroc-inmerf; vep-lit-20261014-eval-livesey2025-clinical-auroc-lassie; vep-lit-20261014-eval-livesey2025-clinical-auroc-list-s2; vep-lit-20261014-eval-livesey2025-clinical-auroc-lrt; vep-lit-20261014-eval-livesey2025-clinical-auroc-m-cap; vep-lit-20261014-eval-livesey2025-clinical-auroc-maverick-benign; vep-lit-20261014-eval-livesey2025-clinical-auroc-metalr; vep-lit-20261014-eval-livesey2025-clinical-auroc-metarnn; vep-lit-20261014-eval-livesey2025-clinical-auroc-metasvm; vep-lit-20261014-eval-livesey2025-clinical-auroc-mistic; vep-lit-20261014-eval-livesey2025-clinical-auroc-moipred-benign; vep-lit-20261014-eval-livesey2025-clinical-auroc-mpc; vep-lit-20261014-eval-livesey2025-clinical-auroc-mutationassessor; vep-lit-20261014-eval-livesey2025-clinical-auroc-mutationtcn; vep-lit-20261014-eval-livesey2025-clinical-auroc-mutformer; vep-lit-20261014-eval-livesey2025-clinical-auroc-mutpred; vep-lit-20261014-eval-livesey2025-clinical-auroc-mutscore; vep-lit-20261014-eval-livesey2025-clinical-auroc-mvp; vep-lit-20261014-eval-livesey2025-clinical-auroc-mvppt; vep-lit-20261014-eval-livesey2025-clinical-auroc-phact; vep-lit-20261014-eval-livesey2025-clinical-auroc-phactboost; vep-lit-20261014-eval-livesey2025-clinical-auroc-phastcons; vep-lit-20261014-eval-livesey2025-clinical-auroc-phd-snpg; vep-lit-20261014-eval-livesey2025-clinical-auroc-phylop; vep-lit-20261014-eval-livesey2025-clinical-auroc-ponp2; vep-lit-20261014-eval-livesey2025-clinical-auroc-popeve; vep-lit-20261014-eval-livesey2025-clinical-auroc-primateai; vep-lit-20261014-eval-livesey2025-clinical-auroc-protgpt2; vep-lit-20261014-eval-livesey2025-clinical-auroc-provean; vep-lit-20261014-eval-livesey2025-clinical-auroc-revel; vep-lit-20261014-eval-livesey2025-clinical-auroc-rhapsody; vep-lit-20261014-eval-livesey2025-clinical-auroc-saprot; vep-lit-20261014-eval-livesey2025-clinical-auroc-sequence-unet; vep-lit-20261014-eval-livesey2025-clinical-auroc-sift; vep-lit-20261014-eval-livesey2025-clinical-auroc-sift4g; vep-lit-20261014-eval-livesey2025-clinical-auroc-sigma; vep-lit-20261014-eval-livesey2025-clinical-auroc-siphy; vep-lit-20261014-eval-livesey2025-clinical-auroc-snap2; vep-lit-20261014-eval-livesey2025-clinical-auroc-snpred; vep-lit-20261014-eval-livesey2025-clinical-auroc-spri; vep-lit-20261014-eval-livesey2025-clinical-auroc-suspect; vep-lit-20261014-eval-livesey2025-clinical-auroc-tranception; vep-lit-20261014-eval-livesey2025-clinical-auroc-uneecon; vep-lit-20261014-eval-livesey2025-clinical-auroc-varity-er; vep-lit-20261014-eval-livesey2025-clinical-auroc-varity-r; vep-lit-20261014-eval-livesey2025-clinical-auroc-vespa; vep-lit-20261014-eval-livesey2025-clinical-auroc-vespal; vep-lit-20261014-eval-livesey2025-clinical-auroc-vest4
pins
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