CAPN12 p.Ala412=
c.1236A>C · rs1321861720 · VCV3056534
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2%, mid)
Conditions
1
CAPN12-related disorder
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 -12 | GERP -4 |
| Overall | ||
| CADD | 0.614 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2%
Middle Eastern · 31/1,550 alleles
Filtering AF
1.74%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.73%
Overall
1.38%
6,814/493,436 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2% | 50 |
| East Asian | 1.79% | 56 |
| European (non-Finnish) | 1.78% | 56 |
| Remaining individualsnot grpmax-eligible | 1.67% | 60 |
| Ashkenazi Jewishnot grpmax-eligible | 0.964% | 104 |
| African / African-American | 0.733% | 136 |
| Finnishnot grpmax-eligible | 0.39% | 256 |
| Admixed American | 0.258% | 387 |
| South Asian | 0.247% | 405 |
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
- CAPN12
- Protein
- p.Ala412=
- Coding
- c.1236A>C
- MANE Select
- NM_144691
- dbSNP
- rs1321861720
- Type
- single nucleotide variant
- Location
- chr19:38737282 (GRCh38)
- Gene constraint
- LOEUF 1.398 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.63
- Residue 412
- the 'domain iii' region; the 'disordered' region
Disease context
CAPN12-related disorder
Similar variants
- CAPN12 c.1627-6C>A Uncertain significance ★ same condition
- CAPN12 p.Gln626Ter Uncertain significance ★ same condition
- CAPN12 p.Phe139Val Uncertain significance ★ ⚠ same condition
- CAPN12 p.Trp363Arg Uncertain significance ⚠ same condition
- CAPN12 c.1583+9C>T Likely benign same condition
- CAPN12 c.1879-3C>T Likely benign same condition
- CAPN12 c.561-7C>T Likely benign same condition
- CAPN12 p.Ala110= Benign same condition
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/capn12-p-ala412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown