EPB41 p.His620=
c.1860C>T · VCV4707308
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.165%, 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 4.8 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 10.62 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.165%
Middle Eastern · 10/6,062 alleles
Filtering AF
0.0895%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0681%
Overall
0.0049%
79/1,613,688 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.165% | 606 |
| European (non-Finnish) | 0.00534% | 18,726 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,830 |
| Admixed American | 0.00333% | 29,996 |
| African / African-American | 0.00133% | 75,040 |
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.His620=
- Coding
- c.1860C>T
- MANE Select
- NM_001376013
- Type
- single nucleotide variant
- Location
- chr1:29058603 (GRCh38)
- Gene constraint
- LOEUF 0.738 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.72 · 3 PDB
- Residue 620
- the 'spectrin--actin-binding' 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-his620 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown