EPHB4 p.Tyr581=
c.1743T>C · rs116240595 · VCV778328
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.03%, afr)
Conditions
3
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 0.1 | GERP -3.2, phastCons 0.22 |
| Overall | ||
| CADD | 4.248 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.03%
African / African-American · 2,274/74,986 alleles
Filtering AF
2.93%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.89%
Overall
0.166%
2,684/1,613,998 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.03% | 33 |
| Middle Eastern | 0.33% | 303 |
| Remaining individualsnot grpmax-eligible | 0.272% | 368 |
| Admixed American | 0.237% | 422 |
| European (non-Finnish) | 0.00619% | 16,165 |
| South Asian | 0.00439% | 22,770 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
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.Tyr581=
- Coding
- c.1743T>C
- MANE Select
- NM_004444
- dbSNP
- rs116240595
- Type
- single nucleotide variant
- Location
- chr7:100813665 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 581
- a UniProt-annotated variant site (in cmavm2)
Similar variants
- EPHB4 c.2484+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Arg365Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Arg739Gln Pathogenic ★★ same condition
- EPHB4 p.Arg739Ter Pathogenic ★★ same condition
- EPHB4 p.Arg763Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Gln580Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Glu664Lys Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Ser280Ter Pathogenic/Likely pathogenic ★★ 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-tyr581 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown