EPHB4 p.Pro843=
c.2529A>C · VCV3845465
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00462%, eas)
Conditions
1
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.62 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.17 | GERP -5, phastCons 0.032 |
| Overall | ||
| CADD | 9.798 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00462%
East Asian · 2/43,318 alleles
Filtering AF
0.000765%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000286%
Overall
0.000144%
2/1,385,314 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.Pro843=
- Coding
- c.2529A>C
- MANE Select
- NM_004444
- Type
- single nucleotide variant
- Location
- chr7:100805650 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 843
- a UniProt-annotated variant site (in cmavm2); the protein kinase domain
Similar variants
- EPHB4 p.Pro843Arg 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-pro843 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown