CAPN1 p.Ala381=
c.1143G>A · VCV3910893
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00572%, sas)
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 -15 | GERP -5.2 |
| Overall | ||
| CADD | 7.774 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00572%
South Asian · 5/87,400 alleles
Filtering AF
0.00217%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00141%
Overall
0.00139%
22/1,582,994 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00572% | 17,480 |
| East Asian | 0.00234% | 42,714 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,314 |
| African / African-American | 0.00135% | 73,978 |
| European (non-Finnish) | 0.0012% | 83,215 |
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
- CAPN1
- Protein
- p.Ala381=
- Coding
- c.1143G>A
- MANE Select
- NM_005186
- Type
- single nucleotide variant
- Location
- chr11:65188724 (GRCh38)
- Gene constraint
- LOEUF 0.977 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.03 · 5 PDB
- Residue 381
- the 'domain iii' region
Similar variants
- CAPN1 p.Ala381Val Pathogenic ★ same residue
- CAPN1 c.1605+5G>A Pathogenic/Likely pathogenic ★★ same type
- CAPN1 c.267+2T>C Pathogenic/Likely pathogenic ★★ same type
- CAPN1 c.338-1G>A Pathogenic ★★ same type
- CAPN1 c.759+1G>A Pathogenic ★★ same type
- CAPN1 c.843+1G>C Pathogenic/Likely pathogenic ★★ same type
- CAPN1 c.929+2T>A Likely pathogenic ★★ same type
- CAPN1 p.Arg285Ter 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/capn1-p-ala381 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown