EPB42 p.Ser248=
c.744C>T · rs138033246 · VCV2715051
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0616%, amr)
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 -3.6 | GERP -5.1 |
| Overall | ||
| CADD | 2.795 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0616%
Admixed American · 37/60,026 alleles
Filtering AF
0.0459%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0405%
Overall
0.0039%
63/1,614,098 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0616% | 1,622 |
| African / African-American | 0.0173% | 5,775 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,417 |
| European (non-Finnish) | 0.000593% | 168,573 |
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.Ser248=
- Coding
- c.744C>T
- MANE Select
- NM_001114134
- dbSNP
- rs138033246
- Type
- single nucleotide variant
- Location
- chr15:43209362 (GRCh38)
- Gene constraint
- LOEUF 0.771 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.35 · 13 PDB
- Residue 248
- a modified residue (phosphoserine; by pka); an α-helix
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-ser248 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown