Evidence claim

Relevance of vep-uc-20261014-protocol-pejaver2022-intervals to use-case-missense-pp3-bp4-calibrated-evidence

Use case: Use calibrated computational evidence for missense variants (PP3/BP4)
Assessed by: PP3/BP4 score intervals per evidence strength (Pejaver et al. 2022 Table 2)
Relevance: Direct evidence
Endpoint: Score interval per ACMG/AMP evidence strength (BP4 and PP3, Supporting to Very Strong) for 13 missense predictors, ClinGen SVI calibration on ClinVar 2019 missense variants

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

13 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.

57 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-10-22-1b7cf027e4f6
Property and statement	Original source and location	Review and provenance
Citation locations 3 values source id vep-uc-20261014-source-pejaver2022 locator Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25 source id vep-uc-20261014-source-tejura2024 locator Summary source id vep-uc-20261014-source-stenton2024 locator Table 1 Context-only references	Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC9748256 (Am J Hum Genet 2022;109(12):2163) Retrieved: 2026-10-14T14:44:42Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.citation_locators` Source artifact SHA-256: `a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b` Hash scope: Exact downloaded bytes, before optional gzip storage
Citation locations 3 values source id vep-uc-20261014-source-pejaver2022 locator Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25 source id vep-uc-20261014-source-tejura2024 locator Summary source id vep-uc-20261014-source-stenton2024 locator Table 1 Context-only references	Stenton et al. 2024, Genet Med 26:101213 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC11560577, NIH author manuscript of Genet Med 2024;26(11):101213 Retrieved: 2026-10-14T14:49:14Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.citation_locators` Source artifact SHA-256: `debe1ae8e304ac0a6272c093bcf7874977e7b9b3921dbe7f5ba096701611ebe7` Hash scope: artifact_sha256 is the SHA-256 of the retrieved page with the two per-request tokens blanked (the content of <meta name="ncbi_phid"> and the csrfmiddlewaretoken value), computed by data/omics/vep-use-cases-20261014/extract/pmc_html.py. The page is a mutable website: this hash describes the retrievals of 2026-10-14 (the collector's, and two by the reviewer, gave the same normalised hash); a later change to the page would change it. The raw bytes of the 2026-10-14 retrieval hashed to c39211252470dbf0f2c8f0c43506f0a66fc868c06c34cc5bee56d77fb344037d.
Citation locations 3 values source id vep-uc-20261014-source-pejaver2022 locator Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25 source id vep-uc-20261014-source-tejura2024 locator Summary source id vep-uc-20261014-source-stenton2024 locator Table 1 Context-only references	Tejura et al. 2024, Am J Hum Genet 111:2031 (PMC) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC11393694 (Am J Hum Genet 2024;111(9):2031) Retrieved: 2026-10-14T14:49:15Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.citation_locators` Source artifact SHA-256: `e00fb418efba3924e47db1aba3be26835dbdbb9f0a4c14aca06a61215ca16ecf` Hash scope: artifact_sha256 is the SHA-256 of the retrieved page with the two per-request tokens blanked (the content of <meta name="ncbi_phid"> and the csrfmiddlewaretoken value), computed by data/omics/vep-use-cases-20261014/extract/pmc_html.py. The page is a mutable website: this hash describes the retrievals of 2026-10-14 (the collector's, and two by the reviewer, gave the same normalised hash); a later change to the page would change it. The raw bytes of the 2026-10-14 retrieval hashed to d84ecae985d9c3362e0b83596b7df28a13c8007230389a9a8f48fa9e1ba1178f.
Comparison group clingen-svi-pp3-bp4-calibration Context-only references	Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC9748256 (Am J Hum Genet 2022;109(12):2163) Retrieved: 2026-10-14T14:44:42Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_group` Source artifact SHA-256: `a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b` Hash scope: Exact downloaded bytes, before optional gzip storage
Comparison group clingen-svi-pp3-bp4-calibration Context-only references	Stenton et al. 2024, Genet Med 26:101213 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC11560577, NIH author manuscript of Genet Med 2024;26(11):101213 Retrieved: 2026-10-14T14:49:14Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_group` Source artifact SHA-256: `debe1ae8e304ac0a6272c093bcf7874977e7b9b3921dbe7f5ba096701611ebe7` Hash scope: artifact_sha256 is the SHA-256 of the retrieved page with the two per-request tokens blanked (the content of <meta name="ncbi_phid"> and the csrfmiddlewaretoken value), computed by data/omics/vep-use-cases-20261014/extract/pmc_html.py. The page is a mutable website: this hash describes the retrievals of 2026-10-14 (the collector's, and two by the reviewer, gave the same normalised hash); a later change to the page would change it. The raw bytes of the 2026-10-14 retrieval hashed to c39211252470dbf0f2c8f0c43506f0a66fc868c06c34cc5bee56d77fb344037d.
Comparison group clingen-svi-pp3-bp4-calibration Context-only references	Tejura et al. 2024, Am J Hum Genet 111:2031 (PMC) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC11393694 (Am J Hum Genet 2024;111(9):2031) Retrieved: 2026-10-14T14:49:15Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_group` Source artifact SHA-256: `e00fb418efba3924e47db1aba3be26835dbdbb9f0a4c14aca06a61215ca16ecf` Hash scope: artifact_sha256 is the SHA-256 of the retrieved page with the two per-request tokens blanked (the content of <meta name="ncbi_phid"> and the csrfmiddlewaretoken value), computed by data/omics/vep-use-cases-20261014/extract/pmc_html.py. The page is a mutable website: this hash describes the retrievals of 2026-10-14 (the collector's, and two by the reviewer, gave the same normalised hash); a later change to the page would change it. The raw bytes of the 2026-10-14 retrieval hashed to d84ecae985d9c3362e0b83596b7df28a13c8007230389a9a8f48fa9e1ba1178f.
Comparison title ClinGen SVI PP3/BP4 calibrations Context-only references	Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC9748256 (Am J Hum Genet 2022;109(12):2163) Retrieved: 2026-10-14T14:44:42Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_title` Source artifact SHA-256: `a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b` Hash scope: Exact downloaded bytes, before optional gzip storage
Comparison title ClinGen SVI PP3/BP4 calibrations Context-only references	Stenton et al. 2024, Genet Med 26:101213 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC11560577, NIH author manuscript of Genet Med 2024;26(11):101213 Retrieved: 2026-10-14T14:49:14Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_title` Source artifact SHA-256: `debe1ae8e304ac0a6272c093bcf7874977e7b9b3921dbe7f5ba096701611ebe7` Hash scope: artifact_sha256 is the SHA-256 of the retrieved page with the two per-request tokens blanked (the content of <meta name="ncbi_phid"> and the csrfmiddlewaretoken value), computed by data/omics/vep-use-cases-20261014/extract/pmc_html.py. The page is a mutable website: this hash describes the retrievals of 2026-10-14 (the collector's, and two by the reviewer, gave the same normalised hash); a later change to the page would change it. The raw bytes of the 2026-10-14 retrieval hashed to c39211252470dbf0f2c8f0c43506f0a66fc868c06c34cc5bee56d77fb344037d.
Comparison title ClinGen SVI PP3/BP4 calibrations Context-only references	Tejura et al. 2024, Am J Hum Genet 111:2031 (PMC) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC11393694 (Am J Hum Genet 2024;111(9):2031) Retrieved: 2026-10-14T14:49:15Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_title` Source artifact SHA-256: `e00fb418efba3924e47db1aba3be26835dbdbb9f0a4c14aca06a61215ca16ecf` Hash scope: artifact_sha256 is the SHA-256 of the retrieved page with the two per-request tokens blanked (the content of <meta name="ncbi_phid"> and the csrfmiddlewaretoken value), computed by data/omics/vep-use-cases-20261014/extract/pmc_html.py. The page is a mutable website: this hash describes the retrievals of 2026-10-14 (the collector's, and two by the reviewer, gave the same normalised hash); a later change to the page would change it. The raw bytes of the 2026-10-14 retrieval hashed to d84ecae985d9c3362e0b83596b7df28a13c8007230389a9a8f48fa9e1ba1178f.
Constraints 4 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. numeric_value of an interval result is the bound a score must reach for that strength; read printed_value for the interval itself. Context-only references	Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) Original source ↗ vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC9748256 (Am J Hum Genet 2022;109(12):2163) Retrieved: 2026-10-14T14:44:42Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.constraints` Source artifact SHA-256: `a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b` Hash scope: Exact downloaded bytes, before optional gzip storage

How to read the evidence

Sources and history

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

3 source records and release history

Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) · Original source · PMC9748256 (Am J Hum Genet 2022;109(12):2163)
Stenton et al. 2024, Genet Med 26:101213 (PMC author manuscript) · Original source · PMC11560577, NIH author manuscript of Genet Med 2024;26(11):101213
Tejura et al. 2024, Am J Hum Genet 111:2031 (PMC) · Original source · PMC11393694 (Am J Hum Genet 2024;111(9):2031)

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Technical metadata and extraction receipts

Stable ID: use-case-mapping-vep-uc-20261014-missense-pp3-bp4-calibrated-evidence-pejaver2022-intervals

field: links:assessed_by:vep-uc-20261014-protocol-pejaver2022-intervals
value: vep-uc-20261014-protocol-pejaver2022-intervals
relevance: direct
endpoint: Score interval per ACMG/AMP evidence strength (BP4 and PP3, Supporting to Very Strong) for 13 missense predictors, ClinGen SVI calibration on ClinVar 2019 missense variants
rationale: Direct: these are the calibrated thresholds the use case asks for, from the calibration behind the ClinGen PP3/BP4 recommendation, for predictors usable in any gene.
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.; numeric_value of an interval result is the bound a score must reach for that strength; read printed_value for the interval itself.
limitations: Calibration is an average over genes; Tejura et al. 2024 found that about 70% of the gene-level REVEL and BayesDel intervals with enough control variants exceeded the incorrect predictions the genome-wide recommendations imply (Summary).; The developers of BayesDel, MutPred2, REVEL and VEST4, the four tools that reach PP3_Strong, and of MPC are authors of Pejaver et al. 2022; those evaluations are recorded as author_reported.; Table S1 point estimates and confidence bounds were not retrieved; only the printed intervals are recorded.; Labels are ClinVar classifications, which the authors assume were not driven by computational evidence (Stenton et al. 2024, Table 1).; Training variants were removed only for BayesDel, FATHMM, MPC, MutPred2, PolyPhen-2, REVEL and VEST4 (and the meta-predictors' constituents) where available; no removal is stated for the other six tools (Methods).; Calibration variants may not represent the novel variants to be classified (Stenton et al. 2024, Table 1).; Transcribed from the source; no reproduction by Rewire and no human scientific review.
citation locators: source id: vep-uc-20261014-source-pejaver2022; locator: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; source id: vep-uc-20261014-source-tejura2024; locator: Summary; source id: vep-uc-20261014-source-stenton2024; locator: Table 1
source locator: vep-uc-20261014-source-pejaver2022: Table 2 and footnote; Methods; author list; references 13, 18, 19, 23, 25; vep-uc-20261014-source-tejura2024: Summary; vep-uc-20261014-source-stenton2024: Table 1
headline metric: evidence-strength-score-interval
comparison group: clingen-svi-pp3-bp4-calibration
comparison title: ClinGen SVI PP3/BP4 calibrations
stratum label: Pejaver et al. 2022: four-level intervals, 13 tools
stratum order: 1
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-uc-20261014-eval-pejaver2022-intervals-bayesdel; vep-uc-20261014-eval-pejaver2022-intervals-cadd; vep-uc-20261014-eval-pejaver2022-intervals-ea; vep-uc-20261014-eval-pejaver2022-intervals-fathmm; vep-uc-20261014-eval-pejaver2022-intervals-gerp; vep-uc-20261014-eval-pejaver2022-intervals-mpc; vep-uc-20261014-eval-pejaver2022-intervals-mutpred2; vep-uc-20261014-eval-pejaver2022-intervals-phylop; vep-uc-20261014-eval-pejaver2022-intervals-polyphen2; vep-uc-20261014-eval-pejaver2022-intervals-primateai; vep-uc-20261014-eval-pejaver2022-intervals-revel; vep-uc-20261014-eval-pejaver2022-intervals-sift; vep-uc-20261014-eval-pejaver2022-intervals-vest4
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subject: Use calibrated computational evidence for missense variants (PP3/BP4)

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