Protocol

Zero-shot ClinVar coding non-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 non-SNVs, highly conserved stratum, AUROC and AUPRC.

15 evaluations · 30 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.

15 recorded evaluations, 30 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

15 evaluations · 30 results. Different protocols are not a single leaderboard.

Protocol: Zero-shot ClinVar coding non-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 non-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 non-SNVs, highly conserved)	AUROC (zero-shot; ClinVar coding non-SNVs, highly conserved)
ESM-1b (Evo 2 paper variant effect evaluations)Evaluation	0.986 (best in column)	0.832
Evo 2 7B (Evo 2 paper variant effect evaluations)Evaluation	0.981	0.829
Evo 2 7B base (Evo 2 paper variant effect evaluations)Evaluation	0.98	0.846 (best in column)
Evo 2 40B base (Evo 2 paper variant effect evaluations)Evaluation	0.975	0.801
Evo 2 40B (Evo 2 paper variant effect evaluations)Evaluation	0.974	0.79
DeCodon 200M (Evo 2 paper variant effect evaluations)Evaluation	0.973	0.712
PhyloP 100 (Evo 2 paper variant effect evaluations)Evaluation	0.96	0.667
PhyloP 241 (Evo 2 paper variant effect evaluations)Evaluation	0.95	0.598
PhyloP 447 (Evo 2 paper variant effect evaluations)Evaluation	0.949	0.601
ESM-2 650M (Evo 2 paper variant effect evaluations)Evaluation	0.946	0.51
Evo 1 (Evo 2 paper variant effect evaluations)Evaluation	0.943	0.526
CodonBERT 87M (Evo 2 paper variant effect evaluations)Evaluation	0.942	0.509
PhyloP 470 (Evo 2 paper variant effect evaluations)Evaluation	0.939	0.577
NT (Evo 2 paper variant effect evaluations)Evaluation	0.937	0.521
EnCodon 620M (Evo 2 paper variant effect evaluations)Evaluation	0.917	0.67

All 30 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: CodonBERT 87M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.942 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J352, row 352: Model 'CodonBERT 87M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: CodonBERT 87M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.509 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I352, row 352: Model 'CodonBERT 87M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: DeCodon 200M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.973 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J343, row 343: Model 'DeCodon 200M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: DeCodon 200M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.712 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I343, row 343: Model 'DeCodon 200M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: EnCodon 620M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.917 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J344, row 344: Model 'EnCodon 620M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: EnCodon 620M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.67 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I344, row 344: Model 'EnCodon 620M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: ESM-1b (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.986 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J339, row 339: Model 'ESM-1b', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: ESM-1b (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.832 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I339, row 339: Model 'ESM-1b', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: ESM-2 650M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.946 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J351, row 351: Model 'ESM-2 650M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: ESM-2 650M (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.51 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I351, row 351: Model 'ESM-2 650M', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.943 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J349, row 349: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.526 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I349, row 349: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.975 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J341, row 341: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.801 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I341, row 341: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.974 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J342, row 342: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.79 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I342, row 342: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.98 AUPRC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J338, row 338: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.846 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I338, row 338: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-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 non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J340, row 340: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.829 AUROC (zero-shot; ClinVar coding non-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 non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I340, row 340: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: NT (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.937 AUPRC (zero-shot; ClinVar coding non-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 NT on ClinVar coding non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J350, row 350: Model 'NT', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: NT (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.521 AUROC (zero-shot; ClinVar coding non-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 NT on ClinVar coding non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I350, row 350: Model 'NT', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: PhyloP 100 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.96 AUPRC (zero-shot; ClinVar coding non-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 PhyloP 100 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J345, row 345: Model 'PhyloP 100', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'
Configuration: PhyloP 100 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.667 AUROC (zero-shot; ClinVar coding non-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 PhyloP 100 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 I345, row 345: Model 'PhyloP 100', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUROC'
Configuration: PhyloP 241 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar coding non-SNVs, highly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.95 AUPRC (zero-shot; ClinVar coding non-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 PhyloP 241 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 J347, row 347: Model 'PhyloP 241', Data 'ClinVar', Genomic_Feature 'Coding', Variant_Type 'non-SNV', Sub_category 'Highly conserved', column 'AUPRC'

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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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Stable ID: gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-coding-non-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 'non-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 'non-SNV', Sub_category 'Highly conserved'; SI A.3.12 and A.3.13 (page 13); Extended Data Fig. 4
limitations: Positives: 529 pathogenic/likely pathogenic; negatives: 37 benign/likely benign; total 566 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: CodonBERT 87M on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: DeCodon 200M on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: EnCodon 620M on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: ESM-1b on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: ESM-2 650M on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: Evo 1 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 40B base on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 40B on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 7B base on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: Evo 2 7B on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: NT on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 100 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 241 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 447 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)
assessment: PhyloP 470 on ClinVar coding non-SNVs, highly conserved (Evo 2 paper)

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