EPHB4 p.Ala371=
c.1113G>A · rs756836367 · VCV2076727
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0236%, amr)
Conditions
1
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -5 |
| Overall | ||
| CADD | 0.301 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0236%
Admixed American · 14/59,272 alleles
Filtering AF
0.0143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.00149%
24/1,609,762 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0236% | 4,234 |
| Finnishnot grpmax-eligible | 0.00159% | 62,946 |
| South Asian | 0.0011% | 90,800 |
| European (non-Finnish) | 0.000679% | 147,300 |
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
- EPHB4
- Protein
- p.Ala371=
- Coding
- c.1113G>A
- MANE Select
- NM_004444
- dbSNP
- rs756836367
- Type
- single nucleotide variant
- Location
- chr7:100819741 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 371
- a UniProt-annotated variant site (in cmavm2); a UniProt-annotated variant site (in); the fibronectin type-iii 1 domain
Similar variants
- EPHB4 p.Ala371Val Benign/Likely benign ★★ ⚠ same residue
- EPHB4 c.1870+5G>C Uncertain significance ★★ same condition
- EPHB4 p.Ala262Val Uncertain significance ★★ ⚠ same condition
- EPHB4 p.Ala345Gly Uncertain significance ★★ ⚠ same condition
- EPHB4 p.Ala931Thr Uncertain significance ★★ ⚠ same condition
- EPHB4 p.Arg148Trp Uncertain significance ★★ ⚠ same condition
- EPHB4 p.Arg310Gln Uncertain significance ★★ ⚠ same condition
- EPHB4 p.Arg483Gln Uncertain significance ★★ ⚠ same condition
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/ephb4-p-ala371 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown