EPHA4 p.Val255=
c.765A>T · rs147498966 · VCV1661875
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.155%, 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 -0.41 | GERP -5.2, phastCons 0.17 |
| Overall | ||
| CADD | 5.947 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.155%
African / African-American · 116/75,062 alleles
Filtering AF
0.132%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.123%
Overall
0.00799%
129/1,614,238 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.155% | 647 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.00833% | 12,007 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| European (non-Finnish) | 0.000169% | 590,023 |
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
- EPHA4
- Protein
- p.Val255=
- Coding
- c.765A>T
- MANE Select
- NM_004438
- dbSNP
- rs147498966
- Type
- single nucleotide variant
- Location
- chr2:221563789 (GRCh38)
- Gene constraint
- LOEUF 0.256 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.93 · 17 PDB
Similar variants
- EPHA4 p.Ala321Thr Uncertain significance ★★ ⚠ same type
- EPHA4 p.Ala852Val Uncertain significance ★★ ⚠ same type
- EPHA4 p.Arg209Cys Uncertain significance ★★ ⚠ same type
- EPHA4 p.Arg230Gln Uncertain significance ★★ ⚠ same type
- EPHA4 p.Arg466Gln Uncertain significance ★★ ⚠ same type
- EPHA4 p.Arg466Trp Uncertain significance ★★ ⚠ same type
- EPHA4 p.Arg486Gln Uncertain significance ★★ ⚠ same type
- EPHA4 p.Arg573Trp 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/epha4-p-val255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown