Evidence claim

Relevance of vep-uc-20261014-protocol-bergquist2025-point-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 on the points scale (Bergquist et al. 2025 Table 1)
Relevance: Direct evidence
Endpoint: Score interval per point value (−4 to +4, including ±3 and indeterminate) for BayesDel, MutPred2, REVEL, VEST4, AlphaMissense, ESM1b and VARITY_R

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

7 reviewed evaluations

Evidence

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

Evidence table

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38 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 2 values source id vep-uc-20261014-source-bergquist2025 locator Table 1 and caption; Materials and Methods; Results source id vep-uc-20261014-source-tejura2024 locator Summary Context-only references	Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC12208618, NIH author manuscript of Genet Med 2025;27(6):101402 Retrieved: 2026-10-14T14:44:51Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.citation_locators` Source artifact SHA-256: `4fe954451167b5a5717a4c37f4054432e1f02fb59862d0fb909edb525e6bb8e2` 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 214864e7b556fcd7f8344a328a5b42ab5c334703de96063e130406ebe304c2d4.
Citation locations 2 values source id vep-uc-20261014-source-bergquist2025 locator Table 1 and caption; Materials and Methods; Results source id vep-uc-20261014-source-tejura2024 locator Summary Context-only references	Tejura et al. 2024, Am J Hum Genet 111:2031 (PMC) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary 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	Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC12208618, NIH author manuscript of Genet Med 2025;27(6):101402 Retrieved: 2026-10-14T14:44:51Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_group` Source artifact SHA-256: `4fe954451167b5a5717a4c37f4054432e1f02fb59862d0fb909edb525e6bb8e2` 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 214864e7b556fcd7f8344a328a5b42ab5c334703de96063e130406ebe304c2d4.
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-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary 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	Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC12208618, NIH author manuscript of Genet Med 2025;27(6):101402 Retrieved: 2026-10-14T14:44:51Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_title` Source artifact SHA-256: `4fe954451167b5a5717a4c37f4054432e1f02fb59862d0fb909edb525e6bb8e2` 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 214864e7b556fcd7f8344a328a5b42ab5c334703de96063e130406ebe304c2d4.
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-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary 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	Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC12208618, NIH author manuscript of Genet Med 2025;27(6):101402 Retrieved: 2026-10-14T14:44:51Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.constraints` Source artifact SHA-256: `4fe954451167b5a5717a4c37f4054432e1f02fb59862d0fb909edb525e6bb8e2` 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 214864e7b556fcd7f8344a328a5b42ab5c334703de96063e130406ebe304c2d4.
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	Tejura et al. 2024, Am J Hum Genet 111:2031 (PMC) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary 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.constraints` 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.
Endpoint Score interval per point value (−4 to +4, including ±3 and indeterminate) for BayesDel, MutPred2, REVEL, VEST4, AlphaMissense, ESM1b and VARITY_R Context-only references	Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC12208618, NIH author manuscript of Genet Med 2025;27(6):101402 Retrieved: 2026-10-14T14:44:51Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.endpoint` Source artifact SHA-256: `4fe954451167b5a5717a4c37f4054432e1f02fb59862d0fb909edb525e6bb8e2` 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 214864e7b556fcd7f8344a328a5b42ab5c334703de96063e130406ebe304c2d4.
Endpoint Score interval per point value (−4 to +4, including ±3 and indeterminate) for BayesDel, MutPred2, REVEL, VEST4, AlphaMissense, ESM1b and VARITY_R Context-only references	Tejura et al. 2024, Am J Hum Genet 111:2031 (PMC) Original source ↗ vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary 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.endpoint` 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.

How to read the evidence

Sources and history

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

2 source records and release history

Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Original source · PMC12208618, NIH author manuscript of Genet Med 2025;27(6):101402
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-bergquist2025-point-intervals

field: links:assessed_by:vep-uc-20261014-protocol-bergquist2025-point-intervals
value: vep-uc-20261014-protocol-bergquist2025-point-intervals
relevance: direct
endpoint: Score interval per point value (−4 to +4, including ±3 and indeterminate) for BayesDel, MutPred2, REVEL, VEST4, AlphaMissense, ESM1b and VARITY_R
rationale: Direct: extends the ClinGen calibration to three newer predictors with the same data and method, and gives the points-scale intervals.
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 developer thresholds of AlphaMissense (0.564) and ESM1b (−7.5) do not reach Supporting under this calibration (Results).; EVE could not be calibrated reliably (about half the benign variants unscored) and is not included (Results).; MutPred2 and REVEL were co-developed by authors of Bergquist et al. 2025 (V. Pejaver, P. Radivojac). The BayesDel, MutPred2, REVEL and VEST4 rows are carried over from Pejaver et al. 2022, whose authors include the developers of all four.; Some of the previously calibrated tools did not reach the likelihood ratios expected for the 3-point intervals (Results, Fig. 1B).; The authors state that this calibration shares the previous study's limitations, including potential circularities and gene- or disease-specific variability (Discussion).; VARITY was trained on ClinVar; each precomputed score comes from a model that excluded that variant (Materials and Methods).; Transcribed from the source; no reproduction by Rewire and no human scientific review.
citation locators: source id: vep-uc-20261014-source-bergquist2025; locator: Table 1 and caption; Materials and Methods; Results; source id: vep-uc-20261014-source-tejura2024; locator: Summary
source locator: vep-uc-20261014-source-bergquist2025: Table 1 and caption; Materials and Methods; Results; vep-uc-20261014-source-tejura2024: Summary
headline metric: evidence-strength-score-interval
comparison group: clingen-svi-pp3-bp4-calibration
comparison title: ClinGen SVI PP3/BP4 calibrations
stratum label: Bergquist et al. 2025: points scale, 7 tools
stratum order: 2
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-bergquist2025-intervals-alphamissense; vep-uc-20261014-eval-bergquist2025-intervals-bayesdel; vep-uc-20261014-eval-bergquist2025-intervals-esm1b; vep-uc-20261014-eval-bergquist2025-intervals-mutpred2; vep-uc-20261014-eval-bergquist2025-intervals-revel; vep-uc-20261014-eval-bergquist2025-intervals-varity-r; vep-uc-20261014-eval-bergquist2025-intervals-vest4
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