EPHB4 c.52+19G>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00583%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +19 | near-intronic (+19 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.38 | GERP -0.71, phastCons 0.004 |
| Non-coding constraint | Z -1.23 | 1 kb window · o/e 1.09 · regional · uncalibrated |
| Overall | ||
| CADD | 11.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00583%
Admixed American · 3/51,428 alleles
Filtering AF
0.00155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000829%
Overall
0.000456%
7/1,533,816 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00583% | 17,143 |
| Remaining individualsnot grpmax-eligible | 0.00168% | 59,696 |
| South Asian | 0.0012% | 83,452 |
| European (non-Finnish) | 0.000176% | 568,014 |
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+19G>C
- MANE Select
- NM_004444
- Type
- single nucleotide variant
- Location
- chr7:100826960 (GRCh38)
- Gene constraint
- LOEUF 0.645 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 23 PDB
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-c-52-plus-19g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown