CAPN15 p.Ser556=
c.1668C>T · rs147318382 · VCV2645805
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.584%, 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 -4.8 | GERP -2.5 |
| Overall | ||
| CADD | 2.269 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.584%
East Asian · 257/44,024 alleles
Filtering AF
0.525%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.502%
Overall
0.107%
1,702/1,587,882 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.584% | 171 |
| European (non-Finnish) | 0.114% | 875 |
| Finnishnot grpmax-eligible | 0.0833% | 1,201 |
| Remaining individualsnot grpmax-eligible | 0.0616% | 1,623 |
| African / African-American | 0.0214% | 4,668 |
| Admixed American | 0.0119% | 8,380 |
| South Asian | 0.00112% | 89,004 |
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.Ser556=
- Coding
- c.1668C>T
- MANE Select
- NM_005632
- dbSNP
- rs147318382
- Type
- single nucleotide variant
- Location
- chr16:549297 (GRCh38)
- Gene constraint
- LOEUF 0.974 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.65
- Residue 556
- 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-ser556 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown