EPHB3 p.Ile497=
c.1491C>T · rs56102565 · VCV735235
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.202%, 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 -4 | GERP -4.3 |
| Overall | ||
| CADD | 14.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.202%
African / African-American · 151/74,742 alleles
Filtering AF
0.176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.166%
Overall
0.011%
176/1,597,796 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.202% | 495 |
| Middle Eastern | 0.0167% | 5,974 |
| Admixed American | 0.0135% | 7,396 |
| Remaining individualsnot grpmax-eligible | 0.0114% | 8,806 |
| East Asian | 0.00449% | 22,279 |
| European (non-Finnish) | 0.000599% | 167,067 |
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.Ile497=
- Coding
- c.1491C>T
- MANE Select
- NM_004443
- dbSNP
- rs56102565
- Type
- single nucleotide variant
- Location
- chr3:184577669 (GRCh38)
- Gene constraint
- LOEUF 0.435 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 82.62 · 4 PDB
- Residue 497
- the fibronectin type-iii 2 domain
Similar variants
- EPHB3 c.1748+4C>T Benign ★★ same type
- EPHB3 p.Phe689= 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
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-ile497 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown