CAPN15 p.Pro738=
c.2214G>A · VCV4821145
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.22%, 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 -8.7 | GERP -2.8 |
| Overall | ||
| CADD | 2.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.22%
African / African-American · 914/75,020 alleles
Filtering AF
1.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.13%
Overall
0.0793%
1,278/1,610,970 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.22% | 82 |
| Middle Eastern | 0.165% | 606 |
| Admixed American | 0.12% | 833 |
| Remaining individualsnot grpmax-eligible | 0.0945% | 1,058 |
| East Asian | 0.0893% | 1,120 |
| European (non-Finnish) | 0.0149% | 6,697 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,787 |
| South Asian | 0.00549% | 18,208 |
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.Pro738=
- Coding
- c.2214G>A
- MANE Select
- NM_005632
- Type
- single nucleotide variant
- Location
- chr16:551533 (GRCh38)
- Gene constraint
- LOEUF 0.974 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.65
- Residue 738
- 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-pro738 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown