EPHB3 p.Phe689=
c.2067T>C · rs61730730 · VCV782245
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.43%, afr)
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 -1.5 | GERP -2.4 |
| Overall | ||
| CADD | 8.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.43%
African / African-American · 2,560/74,662 alleles
Filtering AF
3.32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.27%
Overall
0.185%
2,978/1,613,202 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.43% | 29 |
| Middle Eastern | 0.33% | 303 |
| Remaining individualsnot grpmax-eligible | 0.28% | 357 |
| Admixed American | 0.252% | 397 |
| South Asian | 0.0121% | 8,277 |
| European (non-Finnish) | 0.00509% | 19,665 |
| East Asian | 0.00223% | 44,796 |
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
- EPHB3
- Protein
- p.Phe689=
- Coding
- c.2067T>C
- MANE Select
- NM_004443
- dbSNP
- rs61730730
- Type
- single nucleotide variant
- Location
- chr3:184579829 (GRCh38)
- Gene constraint
- LOEUF 0.435 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.62 · 4 PDB
- Residue 689
- the protein kinase domain
Similar variants
- EPHB3 c.1748+4C>T Benign ★★ same type
- EPHB3 p.Pro438= Benign ★★ same type
- EPHB3 p.Ala220Thr Uncertain significance ★ ⚠ same type
- EPHB3 p.Ala229Val Uncertain significance ★ ⚠ same type
- EPHB3 p.Ala315Thr Uncertain significance ★ ⚠ same type
- EPHB3 p.Ala332Val Uncertain significance ★ ⚠ same type
- EPHB3 p.Ala442Glu Uncertain significance ★ ⚠ same type
- EPHB3 p.Ala517Thr Uncertain significance ★ ⚠ same type
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/ephb3-p-phe689 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown