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Evidence claim

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

Use case
Use calibrated computational evidence for missense variants (PP3/BP4)
Assessed by
Local likelihood ratio at developer-recommended thresholds (Pejaver et al. 2022 Table 3)
Relevance
Direct evidence
Endpoint
Local positive likelihood ratio at the developer-recommended thresholds of SIFT, PolyPhen-2 and CADD, against the PP3 Supporting cut-off of 2.406

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 and footnote; 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 and footnote; 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 and footnote; 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 and footnote; 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 and footnote; 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
Local positive likelihood ratio at the developer-recommended thresholds of SIFT, PolyPhen-2 and CADD, against the PP3 Supporting cut-off of 2.406
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 and footnote; 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-lr
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 and footnote; 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
likelihood-ratio
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 and footnote; 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
4 values
  • 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).
  • Evidence strength was judged on the point estimate of the likelihood ratio, not its confidence bound (Table 3 footnote).
  • Labels are ClinVar classifications, which the authors assume were not driven by computational evidence (Stenton et al. 2024, Table 1).
  • 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 and footnote; 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
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    fields
    • status
    • name
    • description
    • facets
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    • 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-devlr-cadd
    fields
    • status
    • links
    • attributes.origin
    • attributes.comparison
    sha256
    dd9c0e2a525fb51b56731fcd5d5cc58cd432e44a1b0918a8950271bbb333d706
  • record id
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    fields
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    • attributes.comparison
    sha256
    690d04416c6c9459311f82026c48429b83de8ff88647e909dba6272eb49d2de3
  • record id
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    fields
    • status
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    • attributes.origin
    • attributes.comparison
    sha256
    ff4102d7a131364f85884fae0bb06cd3fd78d9a5ed5a94fdc13e3371e62b253e
  • record id
    vep-uc-20261014-protocol-pejaver2022-developer-threshold-lr
    fields
    • status
    • name
    • description
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    • source_ids
    • links
    • attributes
    sha256
    be4523e75988178c2b9c127f2a65efd79c2b963e7913ab3eea83830d015e977b
  • record id
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    fields
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    sha256
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    fields
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    sha256
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    fields
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    sha256
    9f57cce956d59e36f1df5d785b21a5efdfb975fb9877b7fb182013c4c63ee826
  • 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 and footnote; 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
Direct: tests the common practice of applying developer thresholds as PP3 evidence; none reaches Supporting.
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 and footnote; 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-lr

field
links:assessed_by:vep-uc-20261014-protocol-pejaver2022-developer-threshold-lr
value
vep-uc-20261014-protocol-pejaver2022-developer-threshold-lr
relevance
direct
endpoint
Local positive likelihood ratio at the developer-recommended thresholds of SIFT, PolyPhen-2 and CADD, against the PP3 Supporting cut-off of 2.406
rationale
Direct: tests the common practice of applying developer thresholds as PP3 evidence; none reaches Supporting.
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
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).; Evidence strength was judged on the point estimate of the likelihood ratio, not its confidence bound (Table 3 footnote).; Labels are ClinVar classifications, which the authors assume were not driven by computational evidence (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 3 and footnote; Results 'Investigation of commonly used developer-recommended thresholds'
source locator
vep-uc-20261014-source-pejaver2022: Table 3 and footnote; Results 'Investigation of commonly used developer-recommended thresholds'
headline metric
likelihood-ratio
comparison group
clingen-svi-pp3-bp4-calibration
comparison title
ClinGen SVI PP3/BP4 calibrations
stratum label
Developer thresholds: local likelihood ratio
stratum order
3
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-devlr-cadd; vep-uc-20261014-eval-pejaver2022-devlr-polyphen2; vep-uc-20261014-eval-pejaver2022-devlr-sift
pins
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