CAPN5 p.Phe27=
c.81C>T · rs372486853 · VCV1557869
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, 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 -7.4 | GERP -3.2 |
| Overall | ||
| CADD | 2.633 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,888 alleles
Filtering AF
0.00434%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00161%
26/1,613,438 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,978 |
| Admixed American | 0.00833% | 12,001 |
| South Asian | 0.00549% | 18,218 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| African / African-American | 0.004% | 24,975 |
| European (non-Finnish) | 0.000424% | 236,001 |
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
- CAPN5
- Protein
- p.Phe27=
- Coding
- c.81C>T
- MANE Select
- NM_004055
- dbSNP
- rs372486853
- Type
- single nucleotide variant
- Location
- chr11:77084967 (GRCh38)
- Gene constraint
- LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.71 · 1 PDB
- Residue 27
- the calpain catalytic domain
Similar variants
- HTRA3 p.Ala27Ser Uncertain significance ★ ⚠ same residue
- CAPN5 p.Arg243Leu Pathogenic ★★ ⚠ same type
- CAPN5 p.Arg289Trp Pathogenic ★★ ⚠ same type
- CAPN5 p.Ala118Val Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala183Ser Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala185Val Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala237Val Uncertain significance ★★ ⚠ same type
- CAPN5 p.Ala245Val 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/capn5-p-phe27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown