CAPN12 p.Thr421=
c.1263G>A · rs78574604 · VCV1293782
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 9.4%, eas) — too common for a highly-penetrant pathogenic allele
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 0.062 | GERP -4.4, phastCons 0.001 |
| Overall | ||
| CADD | 4.306 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.4%
East Asian · 3,873/41,196 alleles
Filtering AF
9.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.05%
Overall
0.278%
4,315/1,550,230 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 9.4% | 11 |
| Remaining individualsnot grpmax-eligible | 0.417% | 240 |
| South Asian | 0.12% | 833 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0628% | 1,591 |
| Middle Eastern | 0.042% | 2,379 |
| African / African-American | 0.0398% | 2,514 |
| Admixed American | 0.0274% | 3,655 |
| European (non-Finnish) | 0.00244% | 41,000 |
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.Thr421=
- Coding
- c.1263G>A
- MANE Select
- NM_144691
- dbSNP
- rs78574604
- Type
- single nucleotide variant
- Location
- chr19:38737255 (GRCh38)
- Gene constraint
- LOEUF 1.398 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.63
- Residue 421
- the 'domain iii' region
Similar variants
- CAPN12 p.Thr421Met Uncertain significance ★ ⚠ same residue
- CAPN12 c.1362+80A>G Benign ★★ same type
- CAPN12 c.1374+85A>C Benign ★★ same type
- CAPN12 c.1583+12G>A Benign ★★ same type
- CAPN12 c.1584-39C>T Benign ★★ same type
- CAPN12 c.1686+152A>G Benign ★★ same type
- CAPN12 c.1745-17C>T Benign ★★ same type
- CAPN12 c.1815+25G>A Benign ★★ 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/capn12-p-thr421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown