EPHA4 p.Ser270=
c.810C>T · rs764963793 · VCV2198977
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, 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 1.1 | GERP -5.2, phastCons 0.99 |
| Overall | ||
| CADD | 8.235 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,896 alleles
Filtering AF
0.00624%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.00496%
80/1,613,834 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,322 |
| European (non-Finnish) | 0.00542% | 18,436 |
| Admixed American | 0.00333% | 30,004 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| South Asian | 0.0022% | 45,532 |
| Finnishnot grpmax-eligible | 0.00156% | 64,004 |
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.Ser270=
- Coding
- c.810C>T
- MANE Select
- NM_004438
- dbSNP
- rs764963793
- Type
- single nucleotide variant
- Location
- chr2:221563744 (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-ser270 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown