Relevance of vep-lit-20261014-protocol-proteingym-clinical-supervised-substitutions-auc-144fe22 to use-case-brca1-brca2-germline-interpretation

Stable ID: use-case-mapping-vep-lit-20261014-brca1-brca2-germline-interpretation-proteingym-clinical-supervised-substitutions-auc-144fe22

field

links:assessed_by:vep-lit-20261014-protocol-proteingym-clinical-supervised-substitutions-auc-144fe22

value

vep-lit-20261014-protocol-proteingym-clinical-supervised-substitutions-auc-144fe22

relevance

proxy

endpoint

Average over proteins of AUC for supervised clinical predictors (dbNSFP 4.4a), including REVEL and BayesDel

rationale

Proxy: covers the predictors most often used for PP3/BP4 (REVEL, BayesDel), pan-gene; not BRCA-specific.

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

Performance is reported on all available ClinVar labels, so supervised methods whose training data overlap these labels are likely overestimated; models trained on population frequencies leak further, because most ClinVar benign labels rest on observed frequency (ProteinGym paper, 'Clinical datasets', supervised benchmark).; Clinical labels are biased towards heavily studied proteins, such as well-known cancer genes, and towards European ancestry (ProteinGym paper, Limitations).; Evolutionary conservation is one of the criteria used to classify ClinVar variants, so even zero-shot models are not free of circularity (ProteinGym paper, Limitations).; Per-protein AUC averaged over proteins does not test whether scores are comparable across genes.; The ProteinGym paper describes the 2023 clinical sets; whether the sets behind the 144fe22 files are unchanged is not stated.; Whether BRCA1 or BRCA2 is among the clinical proteins is not stated in the summary files.; Transcribed from the source; no reproduction by Rewire and no human scientific review.

citation locators

source id: vep-lit-20261014-source-proteingym-clinical-supervised-substitutions-auc-summary-144fe22; locator: Summary_performance_clinical_substitutions_AUC.csv (supervised); source id: profile-protocol-proteingym-paper-xml-a58110e0; locator: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets' (zero-shot and supervised benchmarks), Appendix A.3.2 'Clinical datasets', Appendix 'Limitations' ('Bias', 'Circularity')

source locator

vep-lit-20261014-source-proteingym-clinical-supervised-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (supervised)

headline metric

auroc

comparison group

proteingym-clinical-144fe22

comparison title

ProteinGym clinical benchmark (commit 144fe22)

stratum label

Substitutions, supervised predictors

stratum order

2

reason

VEP literature pass 2026-10-14: relevance of a newly extracted protocol (rewire-benchmark-data issues #153-#155).

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: 2026-10-14T15:30:00Z; method: ai-assisted-source-review; scope-review; method note: Checked the endpoint against the use case's question, inputs, exclusions and setting in data/entities/use-cases.jsonl; checked each limitation against the cited sources; listed every evaluation on the protocol in reviewed_evaluations after review/check_values.py matched its results.; note: Judgement drafted by the extraction agent and revised in review (docs/reviews/vep-literature-2026-10-14-review.md). Proxy is justified; see the dated review.

reviewed evaluations

vep-lit-20261014-eval-pg-css-proteingym-clinical-bayesdel-addaf; vep-lit-20261014-eval-pg-css-proteingym-clinical-bayesdel-noaf; vep-lit-20261014-eval-pg-css-proteingym-clinical-cadd; vep-lit-20261014-eval-pg-css-proteingym-clinical-clinpred; vep-lit-20261014-eval-pg-css-proteingym-clinical-dann; vep-lit-20261014-eval-pg-css-proteingym-clinical-deogen2; vep-lit-20261014-eval-pg-css-proteingym-clinical-fathmm; vep-lit-20261014-eval-pg-css-proteingym-clinical-gmvp; vep-lit-20261014-eval-pg-css-proteingym-clinical-metarnn; vep-lit-20261014-eval-pg-css-proteingym-clinical-mpc; vep-lit-20261014-eval-pg-css-proteingym-clinical-mutationtaster; vep-lit-20261014-eval-pg-css-proteingym-clinical-polyphen2-hdiv; vep-lit-20261014-eval-pg-css-proteingym-clinical-polyphen2-hvar; vep-lit-20261014-eval-pg-css-proteingym-clinical-revel; vep-lit-20261014-eval-pg-css-proteingym-clinical-varity-er; vep-lit-20261014-eval-pg-css-proteingym-clinical-varity-r; vep-lit-20261014-eval-pg-css-proteingym-clinical-vest4

pins

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• subject: Interpret BRCA1/BRCA2 germline variants