EPHB6 p.Ala658Pro
c.1972G>C · VCV4249991
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0108%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.439 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 29.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0108%
European (non-Finnish) · 128/1,180,016 alleles
Filtering AF
0.00928%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00871%
Overall
0.00818%
132/1,614,024 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0108% | 9,219 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| African / African-American | 0.00134% | 74,894 |
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.Ala658Pro
- Coding
- c.1972G>C
- MANE Select
- NM_004445
- Type
- single nucleotide variant
- Location
- chr7:142868294 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.36 · 1 PDB
Similar variants
- TRPV6 p.Arg390Cys Uncertain significance ★★ ⚠ same type
- EPHB6 p.Arg905Gln Likely benign ★★ same type
- EPHB6 p.Ala341Pro Uncertain significance ★ same type
- EPHB6 p.Ala341Ser Uncertain significance ★ same type
- EPHB6 p.Ala341Thr Uncertain significance ★ same type
- EPHB6 p.Ala453Ser Uncertain significance ★ same type
- EPHB6 p.Ala567Val Uncertain significance ★ same type
- EPHB6 p.Ala617Gly 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-ala658pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown