EPHA5 p.Ala646=
c.1938T>C · rs35363653 · VCV716817
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.68%, afr)
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 4.6 | GERP 0.4, phastCons 1 |
| Overall | ||
| CADD | 9.167 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.68%
African / African-American · 3,505/74,866 alleles
Filtering AF
4.55%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.5%
Overall
0.261%
4,208/1,609,684 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.68% | 21 |
| Middle Eastern | 0.546% | 183 |
| Remaining individualsnot grpmax-eligible | 0.4% | 250 |
| Admixed American | 0.328% | 305 |
| European (non-Finnish) | 0.018% | 5,552 |
| South Asian | 0.0143% | 6,979 |
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
- EPHA5
- Protein
- p.Ala646=
- Coding
- c.1938T>C
- MANE Select
- NM_001281766
- dbSNP
- rs35363653
- Type
- single nucleotide variant
- Location
- chr4:65365981 (GRCh38)
- Gene constraint
- LOEUF 0.711 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.10 · 2 PDB
Similar variants
- EPHA5 c.2173+8T>A Benign ★★ same type
- EPHA5 p.Glu528Gln Benign ★★ ⚠ same type
- EPHA5 p.Ser652Thr Likely benign ★★ ⚠ same type
- EPHA5 c.1794-9583G>A Uncertain significance ★ ⚠ same type
- EPHA5 c.1794-9635T>G Uncertain significance ★ ⚠ same type
- EPHA5 p.Ala123Val Uncertain significance ★ ⚠ same type
- EPHA5 p.Ala332Gly Uncertain significance ★ ⚠ same type
- EPHA5 p.Ala34Thr Uncertain significance ★ ⚠ same type
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/epha5-p-ala646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown