Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 62.9%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
2
capillary malformation-arteriovenous malformation 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +14 | near-intronic (+14 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.28 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.23 | GERP -2.8, phastCons 0.005 |
| Non-coding constraint | Z -1.23 | 1 kb window · o/e 1.09 · regional · uncalibrated |
| Overall | ||
| CADD | 8.425 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
62.9%
East Asian · 24,750/39,378 alleles
Filtering AF
62.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 61.9%
Overall
40.3%
479,250/1,189,970 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 62.9% | 2 |
| Admixed American | 57.6% | 2 |
| Amishnot grpmax-eligible | 51.9% | 2 |
| Middle Eastern | 46.8% | 2 |
| South Asian | 46.8% | 2 |
| Finnishnot grpmax-eligible | 42.1% | 2 |
| Remaining individualsnot grpmax-eligible | 41.7% | 2 |
| European (non-Finnish) | 38.1% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 37.1% | 3 |
| African / African-American | 36.5% | 3 |
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
- Coding
- c.52+14C>G
- MANE Select
- NM_004444
- dbSNP
- rs2304374
- Type
- single nucleotide variant
- Location
- chr7:100826965 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
Similar variants
- EPHB4 c.2484+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Arg365Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Arg739Gln Pathogenic ★★ same condition
- EPHB4 p.Arg739Ter Pathogenic ★★ same condition
- EPHB4 p.Arg763Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Gln580Ter Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Glu664Lys Pathogenic/Likely pathogenic ★★ same condition
- EPHB4 p.Ser280Ter Pathogenic/Likely pathogenic ★★ 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/ephb4-c-52-plus-14c-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown