CAPN15 p.Ala449=
c.1347G>A · rs376305319 · VCV2645801
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0393%, afr)
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 -5.3 | GERP -2.3 |
| Overall | ||
| CADD | 0.091 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0393%
African / African-American · 28/71,298 alleles
Filtering AF
0.0278%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.024%
Overall
0.00418%
64/1,531,296 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0393% | 2,546 |
| Admixed American | 0.0191% | 5,231 |
| Middle Eastern | 0.0171% | 5,860 |
| Remaining individualsnot grpmax-eligible | 0.00845% | 11,832 |
| East Asian | 0.00495% | 20,188 |
| European (non-Finnish) | 0.00167% | 59,996 |
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
- CAPN15
- Protein
- p.Ala449=
- Coding
- c.1347G>A
- MANE Select
- NM_005632
- dbSNP
- rs376305319
- Type
- single nucleotide variant
- Location
- chr16:548185 (GRCh38)
- Gene constraint
- LOEUF 0.974 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.65
Similar variants
- CAPN15 p.Ala449Thr Likely benign ★ same residue
- CAPN15 c.2192+8C>T Uncertain significance ★★ same type
- CAPN15 p.Arg428Trp Uncertain significance ★★ ⚠ same type
- CAPN15 p.Arg867Cys Uncertain significance ★★ ⚠ same type
- CAPN15 p.Arg867His Uncertain significance ★★ ⚠ same type
- CAPN15 p.Cys363Arg Uncertain significance ★★ ⚠ same type
- CAPN15 p.Glu776Ala Uncertain significance ★★ ⚠ same type
- CAPN15 p.Val489Met 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/capn15-p-ala449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown