Protocol

PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1)

Score interval of seven missense predictors for each point value from −4 to +4 of the ACMG/AMP points-based system, including the 3-point level and the indeterminate range.

7 evaluations · 63 results

Overview

An explanatory profile has not yet been reviewed for this record.

Consult the linked sources for architecture or protocol details. Missing evidence is not evidence of a missing capability.

7 recorded evaluations, 63 metric rows. A comparison chart has not yet been validated for these results. The table retains the individual findings and their sources.

View coverage and remaining gaps across all benchmarks

Results

Results are available, but no reviewed comparison panel is linked in this release.

All evaluations

7 evaluations · 63 results. Different protocols are not a single leaderboard.

Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) · Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)

In source order. Decimals are rounded for display; each value links to the printed value and its source.

Tested configuration	Evidence strength score interval (BP4 3 points, ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (BP4 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (BP4 Strong, ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (BP4 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (Indeterminate (0 points), ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (PP3 3 points, ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (PP3 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (PP3 Strong, ClinGen SVI calibration, points scale (Bergquist et al. 2025))	Evidence strength score interval (PP3 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025))
AlphaMissense (Bergquist et al. 2025 calibration)Evaluation	≤ 0.07	[0.071, 0.099]	-	[0.100, 0.169]	[0.170, 0.791]	[0.972, 0.989]	[0.906, 0.971]	≥ 0.99	[0.792, 0.905]
BayesDel (Pejaver et al. 2022 calibration)Evaluation	≤ −0.520	[−0.519, −0.360]	-	[−0.359, −0.180]	[−0.179, 0.129]	[0.410, 0.499]	[0.270, 0.409]	≥ 0.5	[0.130, 0.269]
ESM1b (Bergquist et al. 2025 calibration)Evaluation	≥ 8.8	[−3.1, 8.7]	-	[−6.3, −3.2]	[−10.6, −6.4]	[−23.9, −14.0]	[−13.9, −12.2]	≤ −24.0	[−12.1, −10.7]
MutPred2 (Pejaver et al. 2022 calibration)Evaluation	[0.011, 0.031]	[0.032, 0.197]	≤ 0.01	[0.198, 0.391]	[0.392, 0.736]	[0.895, 0.931]	[0.829, 0.894]	≥ 0.932	[0.737, 0.828]
REVEL (Pejaver et al. 2022 calibration)Evaluation	[0.017, 0.052]	[0.053, 0.183]	≤ 0.016	[0.184, 0.290]	[0.291, 0.643]	[0.879, 0.931]	[0.773, 0.878]	≥ 0.932	[0.644, 0.772]
VARITY_R (Bergquist et al. 2025 calibration)Evaluation	[0.037, 0.063]	[0.064, 0.116]	≤ 0.036	[0.117, 0.251]	[0.252, 0.674]	[0.915, 0.964]	[0.842, 0.914]	≥ 0.965	[0.675, 0.841]
VEST4 (Pejaver et al. 2022 calibration)Evaluation	≤ 0.077	[0.078, 0.302]	-	[0.303, 0.449]	[0.450, 0.763]	[0.909, 0.964]	[0.861, 0.908]	≥ 0.965	[0.764, 0.860]

All 63 result rows with coverage, uncertainty and sources

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Tested model or methodProtocolDatasetEvaluation setupMetricEvidence origin

Applied filters: All linked evaluations

Exact evaluated configurations and original reported results
Tested configuration	Protocol and dataset	Finding	Evidence and details
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.170, 0.791] Evidence strength score interval (Indeterminate (0 points), ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column 'Indeterminate (0)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.100, 0.169] Evidence strength score interval (BP4 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column 'Supporting (−1)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.071, 0.099] Evidence strength score interval (BP4 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column 'Moderate (−2)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	≤ 0.07 Evidence strength score interval (BP4 3 points, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column '(−3)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	- Evidence strength score interval (BP4 Strong, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not applicable: Strength not reached Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column 'Strong (−4)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.792, 0.905] Evidence strength score interval (PP3 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column 'Supporting (+1)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.906, 0.971] Evidence strength score interval (PP3 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column 'Moderate (+2)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.972, 0.989] Evidence strength score interval (PP3 3 points, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column '(+3)'
Configuration: AlphaMissense (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	≥ 0.99 Evidence strength score interval (PP3 Strong, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'AlphaMissense', column 'Strong (+4)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−0.179, 0.129] Evidence strength score interval (Indeterminate (0 points), ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column 'Indeterminate (0)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−0.359, −0.180] Evidence strength score interval (BP4 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column 'Supporting (−1)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−0.519, −0.360] Evidence strength score interval (BP4 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column 'Moderate (−2)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	≤ −0.520 Evidence strength score interval (BP4 3 points, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column '(−3)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	- Evidence strength score interval (BP4 Strong, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not applicable: Strength not reached Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column 'Strong (−4)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.130, 0.269] Evidence strength score interval (PP3 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column 'Supporting (+1)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.270, 0.409] Evidence strength score interval (PP3 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column 'Moderate (+2)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[0.410, 0.499] Evidence strength score interval (PP3 3 points, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column '(+3)'
Configuration: BayesDel (Pejaver et al. 2022 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	≥ 0.5 Evidence strength score interval (PP3 Strong, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'BayesDel', column 'Strong (+4)'
Configuration: ESM1b (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−10.6, −6.4] Evidence strength score interval (Indeterminate (0 points), ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'ESM1b', column 'Indeterminate (0)'
Configuration: ESM1b (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−6.3, −3.2] Evidence strength score interval (BP4 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'ESM1b', column 'Supporting (−1)'
Configuration: ESM1b (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−3.1, 8.7] Evidence strength score interval (BP4 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'ESM1b', column 'Moderate (−2)'
Configuration: ESM1b (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	≥ 8.8 Evidence strength score interval (BP4 3 points, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'ESM1b', column '(−3)'
Configuration: ESM1b (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	- Evidence strength score interval (BP4 Strong, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not applicable: Strength not reached Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'ESM1b', column 'Strong (−4)'
Configuration: ESM1b (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−12.1, −10.7] Evidence strength score interval (PP3 Supporting, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'ESM1b', column 'Supporting (+1)'
Configuration: ESM1b (Bergquist et al. 2025 calibration)	Protocol: PP3/BP4 score intervals on the points scale (Bergquist et al. 2025 Table 1) Dataset: ClinVar 2019 calibration set (Pejaver et al. 2022)	[−13.9, −12.2] Evidence strength score interval (PP3 Moderate, ClinGen SVI calibration, points scale (Bergquist et al. 2025)) unitless · unknown Uncertainty: Not yet extracted: The main text prints no bounds for the thresholds; Figure 1 shows one-sided 95% bootstrap bounds as curves. The Supplementary Material PDF was not retrieved (PMC returned an HTML page on 2026-10-14). Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025) vep-uc-20261014-protocol-bergquist2025-point-intervals Aggregation: Not reported Bergquist et al. 2025, Genet Med 27:101402 (PMC author manuscript) · Table 1, row 'ESM1b', column 'Moderate (+2)'

Source checking is not independent reproduction. Release 2026-10-22-1b7cf027e4f6.

Methods and evaluation design

Procedure, tasks and evaluated configurations

Recorded evaluations

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Baseline coverage

Reference methods help show what a model adds beyond simple controls. We track a null control and a conventional method for each protocol.

0 of 2 active baseline roles have published Rewire measurements in this release. Measurements on a selected protocol do not establish coverage of an entire suite.

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Author-reported evaluations: 4
External evaluations: 3

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This is a suggested selection rule, not a validated method or a measured score.

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Select an upstream conventional reference after reviewing the full protocol

Protocol-specific applicability, permitted inputs, access, split, evaluator and execution requirements need review before implementation or execution.

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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
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)

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Technical metadata and extraction receipts

Stable ID: vep-uc-20261014-protocol-bergquist2025-point-intervals

areas: dna-genomes
contexts: clinical_research
protocol: Same data and calibration as Pejaver et al. 2022; report the score interval for Strong (±4), the 3-point level, Moderate (±2), Supporting (±1) and Indeterminate (0). Very Strong was never reached and is not shown.
task: Calibrated PP3/BP4 score thresholds
metric: evidence-strength-score-interval
metric direction: unknown
unit: unitless
metric implementation: Local posterior probability of pathogenicity estimated in a sliding score window on the ClinVar 2019 set with prior 0.0441; a threshold is the most lenient score at which the one-sided 95% bootstrap bound (10,000 iterations) of the local positive likelihood ratio still reaches the cut-off for that strength (2.406, 5.790, 33.53, 1,124; reciprocals for BP4)
version: Bergquist et al. 2025, Table 1
publication status: peer_reviewed
denominator: 11834
source locator: Table 1 and caption; Materials and Methods
limitations: Calibration is genome-wide (average over genes); Tejura et al. 2024 report that about 70% of the gene-level REVEL and BayesDel intervals with enough control variants exceeded the number of incorrect predictions the genome-wide recommendations imply.; Labels are ClinVar classifications; the authors assume computational evidence had no major role in them (Stenton et al. 2024, Table 1).; AlphaMissense, ESM1b and VARITY_R are calibrated in this paper; the BayesDel, MutPred2, REVEL and VEST4 rows keep the thresholds of Pejaver et al. 2022 and add the 3-point and indeterminate intervals (caption).; No training-set filtering was done for the new tools: only VARITY was trained on ClinVar, and its precomputed score for each variant comes from a model that excluded that variant (Materials and Methods).; The developer thresholds of AlphaMissense (0.564) and ESM1b (−7.5) do not reach Supporting for PP3 or BP4 under this calibration (Results).; V. Pejaver and P. Radivojac (MutPred2; Pejaver also REVEL) are authors. The BayesDel, MutPred2, REVEL and VEST4 rows come 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 when the authors checked them (Results, Fig. 1B).; The caption says Very Strong was never reached, but Pejaver et al. 2022 Table 2 gives a BP4 Very Strong interval for REVEL (≤0.003); here REVEL's Strong (−4) interval, ≤ 0.016, covers both.; The authors state that this calibration shares the limitations of the previous study: representativeness of the data, potential circularities, prior probability estimation and gene- or disease-specific variability (Discussion).
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; artifact sha256: 4fe954451167b5a5717a4c37f4054432e1f02fb59862d0fb909edb525e6bb8e2; retrieval url: https://pmc.ncbi.nlm.nih.gov/articles/PMC12208618/; method: source-hash-verification; ai-assisted-source-review; method note: Checked against the Methods, table captions and author lists of the pinned sources.; note: Checked; see the dated review for rulings on origin and carried-over rows.

Related records

part of: ClinGen SVI calibration of computational predictors for PP3/BP4
uses data: ClinVar 2019 calibration set (Pejaver et al. 2022)
assessed by: Use calibrated computational evidence for missense variants (PP3/BP4)
assessment: AlphaMissense: points-scale PP3/BP4 score intervals (Bergquist et al. 2025)
assessment: BayesDel: points-scale PP3/BP4 score intervals (Bergquist et al. 2025)
assessment: ESM1b: points-scale PP3/BP4 score intervals (Bergquist et al. 2025)
assessment: MutPred2: points-scale PP3/BP4 score intervals (Bergquist et al. 2025)
assessment: REVEL: points-scale PP3/BP4 score intervals (Bergquist et al. 2025)
assessment: VARITY_R: points-scale PP3/BP4 score intervals (Bergquist et al. 2025)
assessment: VEST4: points-scale PP3/BP4 score intervals (Bergquist et al. 2025)

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