EPHA4 p.Ser768=
c.2304C>T · rs2469193438 · VCV2862696
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -0.45 | GERP -5.5, phastCons 0.004 |
| Overall | ||
| CADD | 2.922 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,010 alleles
Overall
0.000137%
2/1,461,872 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,010 |
| European (non-Finnish) | 8.47e-05% | 1,180,004 |
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.Ser768=
- Coding
- c.2304C>T
- MANE Select
- NM_004438
- dbSNP
- rs2469193438
- Type
- single nucleotide variant
- Location
- chr2:221436441 (GRCh38)
- Gene constraint
- LOEUF 0.256 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.93 · 17 PDB
- Residue 768
- the protein kinase domain
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-ser768 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown