EPHB2 p.Ser26=
c.78C>T · VCV3353232
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.128%, 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 -2.8 | GERP -5.1 |
| Overall | ||
| CADD | 2.988 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.128%
African / African-American · 96/74,996 alleles
Filtering AF
0.107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0996%
Overall
0.00762%
123/1,614,024 alleles · rare
exomes 75/1,461,864 · genomes 48/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.128% | 781 |
| Middle Eastern | 0.066% | 1,515 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,683 |
| Admixed American | 0.00833% | 12,001 |
| European (non-Finnish) | 0.000593% | 168,571 |
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.Ser26=
- Coding
- c.78C>T
- MANE Select
- NM_017449
- Type
- single nucleotide variant
- Location
- chr1:22781437 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 5 PDB
- Residue 26
- an α-helix; the eph lbd 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-ser26 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown