EPHA3 p.Val542=
c.1626G>A · rs56330723 · VCV717834
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.234%, nfe)
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 1.4 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 4.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.234%
European (non-Finnish) · 2,756/1,179,598 alleles
Filtering AF
0.226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.223%
Overall
0.185%
2,984/1,613,496 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.234% | 428 |
| Remaining individualsnot grpmax-eligible | 0.139% | 718 |
| Finnishnot grpmax-eligible | 0.125% | 800 |
| Admixed American | 0.0484% | 2,068 |
| African / African-American | 0.036% | 2,777 |
| Middle Eastern | 0.033% | 3,031 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0101% | 9,860 |
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
- EPHA3
- Protein
- p.Val542=
- Coding
- c.1626G>A
- MANE Select
- NM_005233
- dbSNP
- rs56330723
- Type
- single nucleotide variant
- Location
- chr3:89407300 (GRCh38)
- Gene constraint
- LOEUF 0.508 · pLI 0.80 (gnomAD)
- Structure
- AlphaFold pLDDT 81.22 · 28 PDB
Similar variants
- EPHA3 p.Ala777Gly Benign ★★ ⚠ same type
- EPHA3 p.Val597Ile Likely benign ★★ ⚠ same type
- EPHA3 p.Ala182Val Uncertain significance ★ ⚠ same type
- EPHA3 p.Ala427Val Uncertain significance ★ ⚠ same type
- EPHA3 p.Ala546Thr Uncertain significance ★ ⚠ same type
- EPHA3 p.Ala550Pro Uncertain significance ★ ⚠ same type
- EPHA3 p.Ala895Val Uncertain significance ★ ⚠ same type
- EPHA3 p.Arg312Trp 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/epha3-p-val542 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown