EPHB4 p.Asp828=
c.2484C>T · VCV3714926
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0254%, 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 -2.1 | GERP -5 |
| Overall | ||
| CADD | 0.565 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0254%
African / African-American · 19/74,864 alleles
Filtering AF
0.0166%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00205%
33/1,612,686 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0254% | 3,940 |
| Middle Eastern | 0.0164% | 6,080 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,813 |
| East Asian | 0.00446% | 22,429 |
| Admixed American | 0.00167% | 59,880 |
| European (non-Finnish) | 0.000594% | 168,464 |
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
- EPHB4
- Protein
- p.Asp828=
- Coding
- c.2484C>T
- MANE Select
- NM_004444
- Type
- single nucleotide variant
- Location
- chr7:100806420 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
- Residue 828
- an α-helix; a UniProt-annotated variant site (in cmavm2); the protein kinase domain
Similar variants
- EPHB4 c.1691+1G>A Pathogenic/Likely pathogenic ★★ same type
- EPHB4 c.2484+1G>A Pathogenic/Likely pathogenic ★★ same type
- EPHB4 p.Arg269Ter Pathogenic/Likely pathogenic ★★ same type
- EPHB4 p.Arg365Ter Pathogenic/Likely pathogenic ★★ same type
- EPHB4 p.Arg394Ter Pathogenic ★★ same type
- EPHB4 p.Arg431Ter Pathogenic ★★ same type
- EPHB4 p.Arg739Gln Pathogenic ★★ same type
- EPHB4 p.Arg739Ter Pathogenic ★★ 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/ephb4-p-asp828 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown