EPHB4 p.Leu190=
c.570G>A · rs776596000 · VCV1749217
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
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 -0.038 | GERP 0.15, phastCons 0.69 |
| Overall | ||
| CADD | 7.264 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,179,886 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000411%
6/1,461,086 alleles · very rare
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.Leu190=
- Coding
- c.570G>A
- MANE Select
- NM_004444
- dbSNP
- rs776596000
- Type
- single nucleotide variant
- Location
- chr7:100822509 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 190
- a β-strand; a UniProt-annotated variant site (in cmavm2); the eph lbd domain
Similar variants
- EPHB4 p.Leu190Arg Uncertain significance ★★ ⚠ 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-leu190 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown