EPHB4 p.Pro881=
c.2643C>A · rs759414784 · VCV1794214
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000352%, 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 -0.42 | GERP -5 |
| Overall | ||
| CADD | 5.431 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000352%
European (non-Finnish) · 4/1,137,396 alleles
Filtering AF
8.2e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.6e-05%
Overall
0.000291%
4/1,373,808 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.Pro881=
- Coding
- c.2643C>A
- MANE Select
- NM_004444
- dbSNP
- rs759414784
- Type
- single nucleotide variant
- Location
- chr7:100805536 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 881
- an α-helix; a UniProt-annotated variant site (in cmavm2); the protein kinase domain
Similar variants
- EPHB4 p.Pro881Ala 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-pro881 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown