CAPN15 p.Ser749=
c.2247C>T · rs142810996 · VCV2645808
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.216%, nfe)
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 -6.7 | GERP -2.8 |
| Overall | ||
| CADD | 0.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.216%
European (non-Finnish) · 2,543/1,179,562 alleles
Filtering AF
0.209%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.206%
Overall
0.169%
2,722/1,611,414 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.216% | 464 |
| Remaining individualsnot grpmax-eligible | 0.135% | 743 |
| Admixed American | 0.06% | 1,667 |
| African / African-American | 0.052% | 1,921 |
| Middle Eastern | 0.0329% | 3,042 |
| South Asian | 0.0143% | 7,006 |
| East Asian | 0.0111% | 8,972 |
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.Ser749=
- Coding
- c.2247C>T
- MANE Select
- NM_005632
- dbSNP
- rs142810996
- Type
- single nucleotide variant
- Location
- chr16:551566 (GRCh38)
- Gene constraint
- LOEUF 0.974 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.65
- Residue 749
- the calpain catalytic domain
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-ser749 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown