EPB41 p.Pro357=
c.1071G>A · VCV4684799
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.172%, afr)
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 1.1 | GERP -5.5, phastCons 0.99 |
| Overall | ||
| CADD | 12.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.172%
African / African-American · 129/75,018 alleles
Filtering AF
0.148%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.139%
Overall
0.0114%
184/1,614,040 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.172% | 582 |
| Middle Eastern | 0.066% | 1,515 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,906 |
| Admixed American | 0.00334% | 29,972 |
| European (non-Finnish) | 0.00263% | 38,065 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
| South Asian | 0.0011% | 91,084 |
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
- EPB41
- Protein
- p.Pro357=
- Coding
- c.1071G>A
- MANE Select
- NM_001376013
- Type
- single nucleotide variant
- Location
- chr1:29018389 (GRCh38)
- Gene constraint
- LOEUF 0.738 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.72 · 3 PDB
- Residue 357
- the ferm domain; a β-strand
Similar variants
- EPB41 p.Pro357Arg Uncertain significance ★ ⚠ same residue
- EPB41 p.Pro357Leu Uncertain significance ★ ⚠ same residue
- EPB41 p.Arg471Ter Pathogenic/Likely pathogenic ★★ same type
- EPB41 p.Arg508Ter Pathogenic/Likely pathogenic ★★ same type
- EPB41 p.Arg554Ter Pathogenic/Likely pathogenic ★★ same type
- EPB41 p.Arg715Ter Pathogenic ★★ same type
- EPB41 p.Gln274Ter Pathogenic ★★ same type
- EPB41 p.Met210Val Pathogenic/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/epb41-p-pro357 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown