CAPN1 p.Tyr225=
c.675C>T · rs371609832 · VCV2970685
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0357%, eas)
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 -12 | GERP -4.8 |
| Overall | ||
| CADD | 1.597 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0357%
East Asian · 16/44,876 alleles
Filtering AF
0.0223%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0182%
Overall
0.00211%
34/1,613,374 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0357% | 2,805 |
| South Asian | 0.00769% | 13,005 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,220 |
| European (non-Finnish) | 0.000763% | 131,076 |
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.Tyr225=
- Coding
- c.675C>T
- MANE Select
- NM_005186
- dbSNP
- rs371609832
- Type
- single nucleotide variant
- Location
- chr11:65186254 (GRCh38)
- Gene constraint
- LOEUF 0.977 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.03 · 5 PDB
- Residue 225
- the calpain catalytic domain; a β-strand
Similar variants
- CAPN1 p.Tyr225His Uncertain significance ★ ⚠ 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-tyr225 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown