Protocol

Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1)

Zero-shot classification of pathogenic/likely pathogenic versus benign/likely benign variants in the ClinVar coding SNVs, not conserved stratum, AUROC and AUPRC.

18 evaluations · 36 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.

18 recorded evaluations, 36 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

18 evaluations · 36 results. Different protocols are not a single leaderboard.

Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) · Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)

Sorted by AUPRC (zero-shot; ClinVar coding SNVs, not conserved) (higher is better). The best value in each column is highlighted. Decimals are rounded for display; each value links to the printed value and its source.

Tested configuration	AUPRC (zero-shot; ClinVar coding SNVs, not conserved)	AUROC (zero-shot; ClinVar coding SNVs, not conserved)
AlphaMissense (Evo 2 paper variant effect evaluations)Evaluation	0.9 (best in column)	0.964 (best in column)
ESM-1b (Evo 2 paper variant effect evaluations)Evaluation	0.802	0.899
GPN-MSA (Evo 2 paper variant effect evaluations)Evaluation	0.762	0.916
CADD (Evo 2 paper variant effect evaluations)Evaluation	0.623	0.88
Evo 2 7B base (Evo 2 paper variant effect evaluations)Evaluation	0.559	0.865
Evo 2 7B (Evo 2 paper variant effect evaluations)Evaluation	0.546	0.877
Evo 2 40B (Evo 2 paper variant effect evaluations)Evaluation	0.52	0.868
Evo 2 40B base (Evo 2 paper variant effect evaluations)Evaluation	0.517	0.881
ESM-2 650M (Evo 2 paper variant effect evaluations)Evaluation	0.493	0.718
DeCodon 200M (Evo 2 paper variant effect evaluations)Evaluation	0.318	0.677
EnCodon 620M (Evo 2 paper variant effect evaluations)Evaluation	0.289	0.659
Evo 1 (Evo 2 paper variant effect evaluations)Evaluation	0.185	0.552
PhyloP 447 (Evo 2 paper variant effect evaluations)Evaluation	0.175	0.506
PhyloP 241 (Evo 2 paper variant effect evaluations)Evaluation	0.169	0.517
PhyloP 100 (Evo 2 paper variant effect evaluations)Evaluation	0.155	0.571
PhyloP 470 (Evo 2 paper variant effect evaluations)Evaluation	0.151	0.552
NT (Evo 2 paper variant effect evaluations)Evaluation	0.144	0.545
CodonBERT 87M (Evo 2 paper variant effect evaluations)Evaluation	0.123	0.533

All 36 result rows with coverage, uncertainty and sources

Filter evaluations

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 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.9 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source AlphaMissense on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J365, row 365: Model 'AlphaMissense', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: AlphaMissense (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.964 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source AlphaMissense on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I365, row 365: Model 'AlphaMissense', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: CADD (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.623 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source CADD on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J369, row 369: Model 'CADD', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: CADD (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.88 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source CADD on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I369, row 369: Model 'CADD', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: CodonBERT 87M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.123 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source CodonBERT 87M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J380, row 380: Model 'CodonBERT 87M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: CodonBERT 87M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.533 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source CodonBERT 87M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I380, row 380: Model 'CodonBERT 87M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: DeCodon 200M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.318 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source DeCodon 200M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J374, row 374: Model 'DeCodon 200M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: DeCodon 200M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.677 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source DeCodon 200M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I374, row 374: Model 'DeCodon 200M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: EnCodon 620M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.289 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source EnCodon 620M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J375, row 375: Model 'EnCodon 620M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: EnCodon 620M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.659 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source EnCodon 620M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I375, row 375: Model 'EnCodon 620M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: ESM-1b (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.802 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source ESM-1b on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J367, row 367: Model 'ESM-1b', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: ESM-1b (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.899 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source ESM-1b on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I367, row 367: Model 'ESM-1b', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: ESM-2 650M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.493 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source ESM-2 650M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J373, row 373: Model 'ESM-2 650M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: ESM-2 650M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.718 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source ESM-2 650M on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I373, row 373: Model 'ESM-2 650M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.185 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 1 on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J378, row 378: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.552 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 1 on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I378, row 378: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.517 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B base on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J368, row 368: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.881 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B base on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I368, row 368: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.52 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J371, row 371: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.868 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I371, row 371: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.559 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B base on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J372, row 372: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.865 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B base on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I372, row 372: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.546 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J370, row 370: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.877 AUROC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I370, row 370: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUROC'
Configuration: GPN-MSA (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, not conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.762 AUPRC (zero-shot; ClinVar coding SNVs, not conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source GPN-MSA on ClinVar coding SNVs, not conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J366, row 366: Model 'GPN-MSA', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved', column 'AUPRC'

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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.

No execution recipe linked to this protocol. Recipe availability does not establish a completed evaluation.

Author-reported evaluations: 18

Literature evidence is not a Rewire measurement. Executed but unpublished runs and private review status are not included.

Null control

Proposed control: requires review

Protocol-valid seeded random ranking; no fitting on assay labels

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

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

Conventional reference

Proposed control: requires review

Established label-free reference with explicitly permitted sequence/MSA inputs

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

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

Protocol coverage CSV (gzip) · Model evaluation matrix (gzip) · Source table (gzip) · Release and checksums (gzip)

Coverage is derived from release 2026-10-22-1b7cf027e4f6. Source citations describe the original records; they do not validate an unreviewed baseline proposal. No results have been generated by this audit.

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Strengths, limitations and unresolved questions

Evidence

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Evidence table

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Claims, original sources and review scope · Release 2026-10-22-1b7cf027e4f6
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Sources and history

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

3 source records and release history

evo2: Journal full-text XML · Original source · Retrieved page snapshot; no immutable publisher revision supplied
Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Original source · Nature 652 (2026), published 2026-03-04; Supplementary Information file 41586_2026_10176_MOESM1_ESM.pdf (73 pages)
Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026) · Original source · Nature 652 (2026), published 2026-03-04; Supplementary Data 1 file 41586_2026_10176_MOESM3_ESM.xlsx

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Technical metadata and extraction receipts

Stable ID: gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-not-conserved

areas: dna-genomes
contexts: research
protocol: Score each variant zero-shot (for Evo 2, the log-likelihood of the variant sequence minus that of the reference over an 8,192-bp genomic window around the variant) and compute AUROC and AUPRC for pathogenic/likely pathogenic versus benign/likely benign variants in the stratum Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved'.
version: As published, Nature 652 (2026), Supplementary Data 1
source locator: Supplementary Data 1 rows with Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Not conserved'; SI A.3.12 and A.3.13 (page 13); Extended Data Fig. 4
limitations: Positives: 131 pathogenic/likely pathogenic; negatives: 894 benign/likely benign; total 1025 variants (Supplementary Data 1).; Label 'Not conserved'; SI A.3.13 names its bins 'weakly conserved' (0 <= phyloP < 0.5) and 'accelerated evolution' (phyloP < 0); the mapping is not stated.; No split: every model scores the same variants zero-shot (SI A.3.12: 'For each benchmark, we score the same variants with all models').; Supervised comparators (AlphaMissense, CADD, SpliceAI, Pangolin) may have been trained on overlapping variants; training overlap is not reported.; No uncertainty is reported.

Related records

part of: Evo 2 paper zero-shot human variant effect evaluations (Brixi et al. 2026)
uses data: ClinVar October 2024 release, filtered (Brixi et al. 2026)
assessment: AlphaMissense on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: CADD on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: CodonBERT 87M on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: DeCodon 200M on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: EnCodon 620M on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: ESM-1b on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: ESM-2 650M on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: Evo 1 on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: Evo 2 40B base on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: Evo 2 40B on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: Evo 2 7B base on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: Evo 2 7B on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: GPN-MSA on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: NT on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: PhyloP 100 on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: PhyloP 241 on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: PhyloP 447 on ClinVar coding SNVs, not conserved (Evo 2 paper)
assessment: PhyloP 470 on ClinVar coding SNVs, not conserved (Evo 2 paper)

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