Protocol

Zero-shot ClinVar coding SNVs, highly 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, highly 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, highly 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, highly 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, highly conserved)	AUROC (zero-shot; ClinVar coding SNVs, highly conserved)
AlphaMissense (Evo 2 paper variant effect evaluations)Evaluation	0.981 (best in column)	0.935 (best in column)
ESM-1b (Evo 2 paper variant effect evaluations)Evaluation	0.967	0.889
CADD (Evo 2 paper variant effect evaluations)Evaluation	0.961	0.883
GPN-MSA (Evo 2 paper variant effect evaluations)Evaluation	0.941	0.824
PhyloP 100 (Evo 2 paper variant effect evaluations)Evaluation	0.922	0.783
Evo 2 40B (Evo 2 paper variant effect evaluations)Evaluation	0.918	0.776
Evo 2 40B base (Evo 2 paper variant effect evaluations)Evaluation	0.916	0.77
Evo 2 7B (Evo 2 paper variant effect evaluations)Evaluation	0.911	0.756
Evo 2 7B base (Evo 2 paper variant effect evaluations)Evaluation	0.91	0.755
ESM-2 650M (Evo 2 paper variant effect evaluations)Evaluation	0.895	0.657
DeCodon 200M (Evo 2 paper variant effect evaluations)Evaluation	0.894	0.672
PhyloP 447 (Evo 2 paper variant effect evaluations)Evaluation	0.894	0.737
PhyloP 470 (Evo 2 paper variant effect evaluations)Evaluation	0.892	0.718
PhyloP 241 (Evo 2 paper variant effect evaluations)Evaluation	0.886	0.717
EnCodon 620M (Evo 2 paper variant effect evaluations)Evaluation	0.874	0.612
Evo 1 (Evo 2 paper variant effect evaluations)Evaluation	0.847	0.558
NT (Evo 2 paper variant effect evaluations)Evaluation	0.797	0.501
CodonBERT 87M (Evo 2 paper variant effect evaluations)Evaluation	0.788	0.535

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, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.981 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J305, row 305: Model 'AlphaMissense', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: AlphaMissense (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.935 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I305, row 305: Model 'AlphaMissense', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: CADD (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.961 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J307, row 307: Model 'CADD', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: CADD (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.883 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I307, row 307: Model 'CADD', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: CodonBERT 87M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.788 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J321, row 321: Model 'CodonBERT 87M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: CodonBERT 87M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.535 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I321, row 321: Model 'CodonBERT 87M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: DeCodon 200M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.894 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J317, row 317: Model 'DeCodon 200M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: DeCodon 200M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.672 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I317, row 317: Model 'DeCodon 200M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: EnCodon 620M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.874 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J319, row 319: Model 'EnCodon 620M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: EnCodon 620M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.612 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I319, row 319: Model 'EnCodon 620M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: ESM-1b (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.967 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J306, row 306: Model 'ESM-1b', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: ESM-1b (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.889 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I306, row 306: Model 'ESM-1b', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: ESM-2 650M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.895 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J318, row 318: Model 'ESM-2 650M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: ESM-2 650M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.657 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I318, row 318: Model 'ESM-2 650M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.847 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J320, row 320: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.558 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I320, row 320: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.916 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J311, row 311: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.77 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I311, row 311: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.918 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J310, row 310: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.776 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I310, row 310: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.91 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J313, row 313: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.755 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I313, row 313: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.911 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J312, row 312: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.756 AUROC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 I312, row 312: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: GPN-MSA (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.941 AUPRC (zero-shot; ClinVar coding SNVs, highly 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, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-snv-highly-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 J308, row 308: Model 'GPN-MSA', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'SNV', Sub_category 'Highly conserved', column 'AUPRC'

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

Methods and evaluation design

Procedure, tasks and evaluated configurations

Recorded evaluations

Each evaluation records what was tested and under which conditions.

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Baseline coverage

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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: 18

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Null control

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Conventional reference

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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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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-highly-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 'Highly 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 'Highly conserved'; SI A.3.12 and A.3.13 (page 13); Extended Data Fig. 4
limitations: Positives: 8546 pathogenic/likely pathogenic; negatives: 2154 benign/likely benign; total 10700 variants (Supplementary Data 1).; phyloP 100-way > 2 (SI A.3.13).; 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, highly conserved (Evo 2 paper)
assessment: CADD on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: CodonBERT 87M on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: DeCodon 200M on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: EnCodon 620M on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: ESM-1b on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: ESM-2 650M on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: Evo 1 on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 40B base on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 40B on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 7B base on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 7B on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: GPN-MSA on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: NT on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 100 on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 241 on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 447 on ClinVar coding SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 470 on ClinVar coding SNVs, highly conserved (Evo 2 paper)

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