EPHA6 p.Pro46Ser
c.136C>T · rs750834459 · VCV2595125
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00171%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 1.28 | unconstrained · MANE · 52 kb · p 0.00021 · regional, not allelic |
| Overall | ||
| CADD | 24.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00171%
Admixed American · 1/58,502 alleles
Filtering AF
0.000294%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000212%
Overall
0.000691%
10/1,447,720 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00171% | 58,502 |
| Finnishnot grpmax-eligible | 0.0016% | 62,662 |
| European (non-Finnish) | 0.000683% | 146,499 |
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
- EPHA6
- Protein
- p.Pro46Ser
- Coding
- c.136C>T
- MANE Select
- NM_001080448
- dbSNP
- rs750834459
- Type
- single nucleotide variant
- Location
- chr3:96814759 (GRCh38)
- Gene constraint
- LOEUF 0.633 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.90
- Residue 46
- the eph lbd domain
Similar variants
- EPHA6 p.Ala805Val Benign ★★ same type
- EPHA6 p.Thr72= Benign ★★ same type
- EPHA6 p.Ala116Val Uncertain significance ★ same type
- EPHA6 p.Ala14Thr Uncertain significance ★ same type
- EPHA6 p.Ala190Val Uncertain significance ★ same type
- EPHA6 p.Ala382Pro Uncertain significance ★ same type
- EPHA6 p.Ala614Val Uncertain significance ★ same type
- EPHA6 p.Ala636Thr 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/epha6-p-pro46ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown