EPB42 p.Ala4=
c.12C>T · VCV4696678
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 0.8 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 10.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000479%
7/1,461,790 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| Admixed American | 0.005% | 20,003 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 0.000169% | 590,005 |
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
- EPB42
- Protein
- p.Ala4=
- Coding
- c.12C>T
- MANE Select
- NM_001114134
- Type
- single nucleotide variant
- Location
- chr15:43216452 (GRCh38)
- Gene constraint
- LOEUF 0.771 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.35 · 13 PDB
Similar variants
- EPB42 p.Arg259Ter Pathogenic/Likely pathogenic ★★ same type
- EPB42 p.Arg310Gln Likely pathogenic ★★ ⚠ same type
- EPB42 c.10+51G>A Uncertain significance ★★ same type
- EPB42 p.Ala353Val Uncertain significance ★★ ⚠ same type
- EPB42 p.Ala51Thr Uncertain significance ★★ ⚠ same type
- EPB42 p.Ala566Thr Uncertain significance ★★ ⚠ same type
- EPB42 p.Arg155Cys Uncertain significance ★★ ⚠ same type
- EPB42 p.Arg287His Uncertain significance ★★ ⚠ 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/epb42-p-ala4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown