EPHB2 p.Thr512=
c.1536C>T · VCV3344495
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.609%, afr)
Conditions
1
EPHB2-related disorder
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 2.7 | GERP -0.57, phastCons 1 |
| Overall | ||
| CADD | 15.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.609%
African / African-American · 457/75,056 alleles
Filtering AF
0.563%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.545%
Overall
0.04%
646/1,614,196 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.609% | 164 |
| Middle Eastern | 0.115% | 866 |
| Remaining individualsnot grpmax-eligible | 0.0704% | 1,421 |
| Admixed American | 0.0533% | 1,876 |
| European (non-Finnish) | 0.00847% | 11,800 |
| East Asian | 0.00446% | 22,438 |
| South Asian | 0.00439% | 22,772 |
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.Thr512=
- Coding
- c.1536C>T
- MANE Select
- NM_017449
- Type
- single nucleotide variant
- Location
- chr1:22892991 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 5 PDB
- Residue 512
- the fibronectin type-iii 2 domain
Disease context
EPHB2-related disorder
Similar variants
- EPHB2 p.Tyr240Asp Uncertain significance ⚠ same condition
- EPHB2 c.968-7G>A Likely benign same condition
- EPHB2 c.*120G>A Likely benign same condition
- EPHB2 c.*213A>G Likely benign same condition
- EPHB2 c.*291C>T Likely benign same condition
- EPHB2 p.Asn755= Likely benign same condition
- EPHB2 p.His583= Likely benign same condition
- EPHB2 p.Phe803= Likely benign 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/ephb2-p-thr512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown