rewirebio.iobenchmarks
← Browse all evidence claims
Evidence claim

Relevance of vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction to use-case-missense-pp3-bp4-calibrated-evidence

Use case
Use calibrated computational evidence for missense variants (PP3/BP4)
Assessed by
Share of gnomAD variants called pathogenic at developer thresholds (Pejaver et al. 2022 Table 3)
Relevance
Proxy evidence
Endpoint
Fraction of the gnomAD reference set called pathogenic by SIFT, PolyPhen-2 and CADD at their developer thresholds, against a 4.41% prior

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

3 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-uc-20261014-source-pejaver2022
    locator
    Table 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'
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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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

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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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 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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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

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		Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML)

Original source ↗

vep-uc-20261014-source-pejaver2022: Table 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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

Endpoint
Fraction of the gnomAD reference set called pathogenic by SIFT, PolyPhen-2 and CADD at their developer thresholds, against a 4.41% prior
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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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.endpoint

Source artifact SHA-256: a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b

Hash scope: Exact downloaded bytes, before optional gzip storage

Claimed field
links:assessed_by:vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction
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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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.field

Source artifact SHA-256: a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b

Hash scope: Exact downloaded bytes, before optional gzip storage

Headline metric
proportion
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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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.headline_metric

Source artifact SHA-256: a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b

Hash scope: Exact downloaded bytes, before optional gzip storage

Limitations
2 values
  • The gnomAD set is unlabelled; a fraction above the prior suggests false positive calls but does not count them.
  • Transcribed from the source; no reproduction by Rewire and no human scientific review.
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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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.limitations

Source artifact SHA-256: a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b

Hash scope: Exact downloaded bytes, before optional gzip storage

Pinned records
9 values
  • record id
    use-case-missense-pp3-bp4-calibrated-evidence
    fields
    • status
    • name
    • description
    • facets
    • attributes.question
    • attributes.decision
    • attributes.inputs
    • attributes.output
    • attributes.exclusions
    • attributes.setting
    • attributes.clinical_scope
    • attributes.intended_users
    sha256
    25250cac852da67b4c4b8ff30fab89588ca97898bcad5ccea87d30e669fea4d1
  • record id
    vep-uc-20261014-eval-pejaver2022-devfraction-cadd
    fields
    • status
    • links
    • attributes.origin
    • attributes.comparison
    sha256
    1caaa6ee1d812a835549b847591d591d1c04d018c48a429ed7c5babfe4d78037
  • record id
    vep-uc-20261014-eval-pejaver2022-devfraction-polyphen2
    fields
    • status
    • links
    • attributes.origin
    • attributes.comparison
    sha256
    4592f175e168cc4a1f3ceee2b9c8f987b3059a2659badea1420a9660bd810e74
  • record id
    vep-uc-20261014-eval-pejaver2022-devfraction-sift
    fields
    • status
    • links
    • attributes.origin
    • attributes.comparison
    sha256
    29f059d3c6549f14684962f7b06b6095eb77cfc884006eed78e54796e8979bc0
  • record id
    vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction
    fields
    • status
    • name
    • description
    • facets
    • source_ids
    • links
    • attributes
    sha256
    f3d69431ce4b99340520b1ba25177570af4e3ba5e4db6a62afefa84472df139b
  • record id
    vep-uc-20261014-result-pejaver2022-devfraction-cadd
    fields
    • status
    • attributes.metric
    • attributes.metric_qualifier
    • attributes.printed_value
    • attributes.numeric_value
    sha256
    dee28a5ecec7c86de84b5a62d2b467ef85da9e73fa28eca8d35c19463674f7a0
  • record id
    vep-uc-20261014-result-pejaver2022-devfraction-polyphen2
    fields
    • status
    • attributes.metric
    • attributes.metric_qualifier
    • attributes.printed_value
    • attributes.numeric_value
    sha256
    81521b5be26176ea9d97b65fddb3bd23d6046294060073c7b52b64959efb46f8
  • record id
    vep-uc-20261014-result-pejaver2022-devfraction-sift
    fields
    • status
    • attributes.metric
    • attributes.metric_qualifier
    • attributes.printed_value
    • attributes.numeric_value
    sha256
    d7b12912809c6896eadd1478b5bfb936dd78672b06dc176b09f6f81f989baf4f
  • record id
    vep-uc-20261014-source-pejaver2022
    fields
    • status
    • attributes.artifact_sha256
    sha256
    c03d149f0fa601968241dc3dc7ece8cf2d8f55d81a2579b0a0fe4597190d77c9
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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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.pins

Source artifact SHA-256: a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b

Hash scope: Exact downloaded bytes, before optional gzip storage

Rationale
Proxy: shows over-calling at uncalibrated thresholds on unlabelled population variants; it is not a measure of evidence strength.
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 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'

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.rationale

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

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-pejaver2022-developer-threshold-gnomad-fraction

field
links:assessed_by:vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction
value
vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction
relevance
proxy
endpoint
Fraction of the gnomAD reference set called pathogenic by SIFT, PolyPhen-2 and CADD at their developer thresholds, against a 4.41% prior
rationale
Proxy: shows over-calling at uncalibrated thresholds on unlabelled population variants; it is not a measure of evidence strength.
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
The gnomAD set is unlabelled; a fraction above the prior suggests false positive calls but does not count them.; Transcribed from the source; no reproduction by Rewire and no human scientific review.
citation locators
source id: vep-uc-20261014-source-pejaver2022; locator: Table 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'
source locator
vep-uc-20261014-source-pejaver2022: Table 3 last column; Results 'Investigation of commonly used developer-recommended thresholds'
headline metric
proportion
comparison group
clingen-svi-pp3-bp4-calibration
comparison title
ClinGen SVI PP3/BP4 calibrations
stratum label
Developer thresholds: gnomAD fraction called pathogenic
stratum order
4
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-devfraction-cadd; vep-uc-20261014-eval-pejaver2022-devfraction-polyphen2; vep-uc-20261014-eval-pejaver2022-devfraction-sift
pins
record id: use-case-missense-pp3-bp4-calibrated-evidence; fields: status; name; description; facets; attributes.question; attributes.decision; attributes.inputs; attributes.output; attributes.exclusions; attributes.setting; attributes.clinical_scope; attributes.intended_users; sha256: 25250cac852da67b4c4b8ff30fab89588ca97898bcad5ccea87d30e669fea4d1; record id: vep-uc-20261014-eval-pejaver2022-devfraction-cadd; fields: status; links; attributes.origin; attributes.comparison; sha256: 1caaa6ee1d812a835549b847591d591d1c04d018c48a429ed7c5babfe4d78037; record id: vep-uc-20261014-eval-pejaver2022-devfraction-polyphen2; fields: status; links; attributes.origin; attributes.comparison; sha256: 4592f175e168cc4a1f3ceee2b9c8f987b3059a2659badea1420a9660bd810e74; record id: vep-uc-20261014-eval-pejaver2022-devfraction-sift; fields: status; links; attributes.origin; attributes.comparison; sha256: 29f059d3c6549f14684962f7b06b6095eb77cfc884006eed78e54796e8979bc0; record id: vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction; fields: status; name; description; facets; source_ids; links; attributes; sha256: f3d69431ce4b99340520b1ba25177570af4e3ba5e4db6a62afefa84472df139b; record id: vep-uc-20261014-result-pejaver2022-devfraction-cadd; fields: status; attributes.metric; attributes.metric_qualifier; attributes.printed_value; attributes.numeric_value; sha256: dee28a5ecec7c86de84b5a62d2b467ef85da9e73fa28eca8d35c19463674f7a0; record id: vep-uc-20261014-result-pejaver2022-devfraction-polyphen2; fields: status; attributes.metric; attributes.metric_qualifier; attributes.printed_value; attributes.numeric_value; sha256: 81521b5be26176ea9d97b65fddb3bd23d6046294060073c7b52b64959efb46f8; record id: vep-uc-20261014-result-pejaver2022-devfraction-sift; fields: status; attributes.metric; attributes.metric_qualifier; attributes.printed_value; attributes.numeric_value; sha256: d7b12912809c6896eadd1478b5bfb936dd78672b06dc176b09f6f81f989baf4f; record id: vep-uc-20261014-source-pejaver2022; fields: status; attributes.artifact_sha256; sha256: c03d149f0fa601968241dc3dc7ece8cf2d8f55d81a2579b0a0fe4597190d77c9
Related records

Suggest a correction