EPHB4 c.52+14del
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 37.3%, mid) — 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 | ||
| Splice region | donor +14 | near-intronic (+14 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.46 | GERP -2.3, phastCons 0.01 |
| Non-coding constraint | Z -1.23 | 1 kb window · o/e 1.09 · regional · uncalibrated |
| Overall | ||
| CADD | 6.544 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
37.3%
Middle Eastern · 2,043/5,482 alleles
Filtering AF
35.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 35.4%
Overall
26.2%
373,477/1,423,328 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 37.3% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 33.4% | 3 |
| Finnishnot grpmax-eligible | 31.1% | 3 |
| European (non-Finnish) | 27.5% | 4 |
| South Asian | 26.1% | 4 |
| Remaining individualsnot grpmax-eligible | 25.4% | 4 |
| African / African-American | 19.2% | 5 |
| Admixed American | 17% | 6 |
| Amishnot grpmax-eligible | 17% | 6 |
| East Asian | 0.333% | 300 |
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+14del
- MANE Select
- NM_004444
- dbSNP
- rs35907339
- Type
- Deletion
- Location
- chr7:100826965 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
Similar variants
- EPHB4 c.124-11_124-9del Uncertain significance ★★ same type
- EPHB4 c.52+14_52+15del Benign ★★ same type
- EPHB4 c.1691_1691+10del Likely pathogenic ★ same type
- EPHB4 c.50_52+2del Likely pathogenic ★ same type
- EPHB4 p.Ala153fs Pathogenic ★ same type
- EPHB4 p.Ala476fs Likely pathogenic ★ same type
- EPHB4 p.Ala800fs Pathogenic ★ same type
- EPHB4 p.Arg240fs Likely 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-c-52-plus-14del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown