EPAS1 p.Ala665=
c.1995G>A · rs755779444 · VCV1784044
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, eas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.5 | GERP -2.6 |
| Overall | ||
| CADD | 0.165 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
East Asian · 9/44,888 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00682%
110/1,613,804 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.02% | 4,988 |
| African / African-American | 0.00801% | 12,484 |
| European (non-Finnish) | 0.00771% | 12,967 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
| Admixed American | 0.00167% | 59,992 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- EPAS1
- Protein
- p.Ala665=
- Coding
- c.1995G>A
- MANE Select
- NM_001430
- dbSNP
- rs755779444
- Type
- single nucleotide variant
- Location
- chr2:46380667 (GRCh38)
- Gene constraint
- LOEUF 0.366 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.41 · 43 PDB
Similar variants
- EPAS1 p.Ala665Val Uncertain significance ★ ⚠ same residue
- EPAS1 p.Ala439Gly Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala463Thr Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala698Pro Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala758Thr Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala81Thr Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala83Asp Uncertain significance ★★ ⚠ same condition
- EPAS1 p.Ala94Val Uncertain significance ★★ ⚠ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/epas1-p-ala665 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown