EPHB6 p.Arg686His
c.2057G>A · rs753358072 · VCV2601138
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.286 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,882 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00779%
Overall
0.00273%
44/1,613,642 alleles · ultra-rare
exomes 43/1,461,500 · genomes 1/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,987 |
| Middle Eastern | 0.0164% | 6,084 |
| European (non-Finnish) | 0.00271% | 36,875 |
| African / African-American | 0.00267% | 37,462 |
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.Arg686His
- Coding
- c.2057G>A
- MANE Select
- NM_004445
- dbSNP
- rs753358072
- Type
- single nucleotide variant
- Location
- chr7:142868510 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.36 · 1 PDB
- Residue 686
- the protein kinase domain
Similar variants
- EPHB6 p.Arg686Leu Uncertain significance ★ same residue
- 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
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-arg686his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown