CACNA1C p.Pro44=
c.132C>T · rs770183452 · VCV416864
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0114%, eas)
Conditions
2
Cardiovascular phenotype
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 -0.93 | GERP 0.011, phastCons 0.002 |
| Overall | ||
| CADD | 8.939 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0114%
East Asian · 5/43,674 alleles
Filtering AF
0.00444%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00292%
Overall
0.000502%
8/1,593,996 alleles · ultra-rare
exomes 6/1,441,748 · genomes 2/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0114% | 8,735 |
| African / African-American | 0.00269% | 37,243 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,754 |
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
- CACNA1C
- Protein
- p.Pro44=
- Coding
- c.132C>T
- MANE Select
- NM_000719
- dbSNP
- rs770183452
- Type
- single nucleotide variant
- Location
- chr12:2115306 (GRCh38)
- Gene constraint
- LOEUF 0.186 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.73 · 33 PDB
Similar variants
- CACNA1C p.Pro44Ala Uncertain significance ★★ same residue
- CACNA1C p.Arg518Cys Pathogenic/Likely pathogenic ★★ same condition
- CACNA1C p.Arg518His Pathogenic/Likely pathogenic ★★ same condition
- CACNA1C p.Arg858His Pathogenic/Likely pathogenic ★★ same condition
- CACNA1C p.Arg860Gly Likely pathogenic ★★ same condition
- CACNA1C p.Arg860Ter Pathogenic ★★ same condition
- CACNA1C p.Asn537Asp Likely pathogenic ★★ same condition
- CACNA1C p.Glu1115Lys Pathogenic/Likely pathogenic ★★ 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/cacna1c-p-pro44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown