EPHB6 p.Gly708Arg
c.2122G>A · rs200244040 · VCV2596719
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0334%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.677 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP 0.89, phastCons 1 |
| Overall | ||
| CADD | 26.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0334%
Admixed American · 20/59,968 alleles
Filtering AF
0.0221%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0184%
Overall
0.00248%
40/1,613,324 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0334% | 2,998 |
| East Asian | 0.00223% | 44,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| European (non-Finnish) | 0.00136% | 73,745 |
| African / African-American | 0.00133% | 74,944 |
| South Asian | 0.0011% | 91,078 |
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.Gly708Arg
- Coding
- c.2122G>A
- MANE Select
- NM_004445
- dbSNP
- rs200244040
- Type
- single nucleotide variant
- Location
- chr7:142868575 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.36 · 1 PDB
- Residue 708
- the protein kinase domain
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-gly708arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown