EPB41 p.Ala11=
c.33C>G · rs142705709 · VCV2638582
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0218%, nfe)
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 -5 | GERP -5.2 |
| Overall | ||
| CADD | 0.158 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0218%
European (non-Finnish) · 257/1,179,992 alleles
Filtering AF
0.0196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0187%
Overall
0.0174%
281/1,613,956 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0218% | 4,591 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.0133% | 7,501 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| South Asian | 0.00549% | 18,213 |
| Finnishnot grpmax-eligible | 0.00469% | 21,329 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| African / African-American | 0.00267% | 37,476 |
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.Ala11=
- Coding
- c.33C>G
- MANE Select
- NM_001376013
- dbSNP
- rs142705709
- Type
- single nucleotide variant
- Location
- chr1:28987470 (GRCh38)
- Gene constraint
- LOEUF 0.738 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.72 · 3 PDB
- Residue 11
- the 'disordered' region
Similar variants
- 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
- EPB41 p.Tyr331Ter Pathogenic/Likely pathogenic ★★ same type
- EPB41 p.Ala259Val 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/epb41-p-ala11 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown