CAPN15 p.Ala199=
c.597G>A · rs377457205 · VCV3052817
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.252%, 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 -5 | GERP -2.4 |
| Overall | ||
| CADD | 0.024 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.252%
Middle Eastern · 15/5,952 alleles
Filtering AF
0.155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.126%
Overall
0.0538%
852/1,583,568 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.252% | 397 |
| Finnishnot grpmax-eligible | 0.238% | 420 |
| Remaining individualsnot grpmax-eligible | 0.0666% | 1,502 |
| European (non-Finnish) | 0.0542% | 1,846 |
| African / African-American | 0.043% | 2,328 |
| Admixed American | 0.0171% | 5,833 |
| South Asian | 0.00449% | 22,263 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00343% | 29,182 |
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.Ala199=
- Coding
- c.597G>A
- MANE Select
- NM_005632
- dbSNP
- rs377457205
- Type
- single nucleotide variant
- Location
- chr16:547435 (GRCh38)
- Gene constraint
- LOEUF 0.974 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.65
- Residue 199
- the 'disordered' region
Similar variants
- 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
- CAPN15 p.Val841Met 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-ala199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown