EPHB2 p.Ile652=
c.1956C>T · rs55927202 · VCV780763
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0292%, nfe)
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 1.9 | GERP 0.57, phastCons 1 |
| Overall | ||
| CADD | 10.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0292%
European (non-Finnish) · 345/1,180,042 alleles
Filtering AF
0.0266%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0256%
Overall
0.0226%
365/1,614,192 alleles · ultra-rare
exomes 340/1,461,886 · genomes 25/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0292% | 3,420 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| Admixed American | 0.00833% | 12,004 |
| African / African-American | 0.00533% | 18,764 |
| Finnishnot grpmax-eligible | 0.00469% | 21,343 |
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
- EPHB2
- Protein
- p.Ile652=
- Coding
- c.1956C>T
- MANE Select
- NM_017449
- dbSNP
- rs55927202
- Type
- single nucleotide variant
- Location
- chr1:22906777 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 5 PDB
- Residue 652
- the protein kinase domain; a β-strand
Similar variants
- EPHB2 p.Val414Ile Uncertain significance ★★ ⚠ same type
- EPHB2 c.1766-9G>T Benign/Likely benign ★★ same type
- EPHB2 p.Ala279Ser Benign ★★ same type
- EPHB2 p.Asn242= Likely benign ★★ same type
- EPHB2 p.Asp574= Benign ★★ same type
- EPHB2 p.Asp678Asn Likely benign ★★ same type
- EPHB2 p.Gln875= Benign ★★ same type
- EPHB2 p.Ser170= Benign ★★ 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/ephb2-p-ile652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown