EPHB2 p.Pro459=
c.1377G>A · rs2229872 · VCV1174978
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 45.9%, eas) — too common for a highly-penetrant pathogenic allele
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 -14 | GERP -5.4 |
| Overall | ||
| CADD | 5.204 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
45.9%
East Asian · 20,581/44,852 alleles
Filtering AF
45.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 45.1%
Overall
10.8%
174,732/1,614,030 alleles · common
exomes 153,967/1,461,792 · genomes 20,765/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 45.9% | 2 |
| African / African-American | 17.5% | 6 |
| Amishnot grpmax-eligible | 14.8% | 7 |
| Admixed American | 13.4% | 7 |
| Remaining individualsnot grpmax-eligible | 12.6% | 8 |
| South Asian | 12.4% | 8 |
| Middle Eastern | 11.5% | 9 |
| Ashkenazi Jewishnot grpmax-eligible | 10.2% | 10 |
| Finnishnot grpmax-eligible | 9.2% | 11 |
| European (non-Finnish) | 8.83% | 11 |
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.Pro459=
- Coding
- c.1377G>A
- MANE Select
- NM_017449
- dbSNP
- rs2229872
- Type
- single nucleotide variant
- Location
- chr1:22882432 (GRCh38)
- Gene constraint
- LOEUF 0.265 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 5 PDB
- Residue 459
- the fibronectin type-iii 2 domain
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-pro459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown