CAPN15 p.Ala615=
c.1845G>A · VCV3349177
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.432%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.36 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -2.4 |
| Overall | ||
| CADD | 0.702 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.432%
African / African-American · 316/73,218 alleles
Filtering AF
0.392%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.377%
Overall
0.0274%
422/1,540,066 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.432% | 232 |
| Admixed American | 0.0878% | 1,139 |
| Remaining individualsnot grpmax-eligible | 0.0351% | 2,851 |
| Middle Eastern | 0.0179% | 5,580 |
| European (non-Finnish) | 0.00314% | 31,863 |
| East Asian | 0.00243% | 41,156 |
| Finnishnot grpmax-eligible | 0.00214% | 46,660 |
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.Ala615=
- Coding
- c.1845G>A
- MANE Select
- NM_005632
- Type
- single nucleotide variant
- Location
- chr16:549617 (GRCh38)
- Gene constraint
- LOEUF 0.974 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.65
- Residue 615
- the calpain catalytic domain
Similar variants
- CAPN15 p.Ala615Ser Uncertain significance ★ ⚠ same residue
- CAPN15 p.Ala615Val Uncertain significance ★ ⚠ 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
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-ala615 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown