EPHB6 p.Ala341Ser
c.1021G>T · rs139843314 · VCV3089684
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0367%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.2 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.29 | GERP -3.5, phastCons 0.005 |
| Overall | ||
| CADD | 0.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0367%
Admixed American · 22/59,990 alleles
Filtering AF
0.0248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.0188%
303/1,613,286 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0367% | 2,727 |
| European (non-Finnish) | 0.0225% | 4,436 |
| Middle Eastern | 0.0165% | 6,050 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,410 |
| Finnishnot grpmax-eligible | 0.0063% | 15,873 |
| African / African-American | 0.00267% | 37,444 |
| South Asian | 0.0022% | 45,532 |
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
- EPHB6
- Protein
- p.Ala341Ser
- Coding
- c.1021G>T
- MANE Select
- NM_004445
- dbSNP
- rs139843314
- Type
- single nucleotide variant
- Location
- chr7:142865546 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.36 · 1 PDB
Similar variants
- EPHB6 p.Ala341Pro Uncertain significance ★ same residue
- EPHB6 p.Ala341Thr Uncertain significance ★ same residue
- TRPV6 p.Arg390Cys Uncertain significance ★★ ⚠ same type
- EPHB6 p.Arg905Gln Likely benign ★★ same type
- EPHB6 p.Ala453Ser Uncertain significance ★ same type
- EPHB6 p.Ala567Val Uncertain significance ★ same type
- EPHB6 p.Ala617Gly Uncertain significance ★ same type
- EPHB6 p.Ala658Pro 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/ephb6-p-ala341ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown