CACNA1C p.Pro2000=
c.6000C>T · rs772160508 · VCV519306
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00988%, sas)
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 0.84 | GERP 1.7, phastCons 0.033 |
| Overall | ||
| CADD | 8.345 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00988%
South Asian · 9/91,076 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.0018%
29/1,613,510 alleles · very rare
exomes 26/1,461,296 · genomes 3/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00988% | 10,120 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.00161% | 62,096 |
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.Pro2000=
- Coding
- c.6000C>T
- MANE Select
- NM_000719
- dbSNP
- rs772160508
- Type
- single nucleotide variant
- Location
- chr12:2688662 (GRCh38)
- Gene constraint
- LOEUF 0.186 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.73 · 33 PDB
- Residue 2000
- a UniProt-annotated variant site (in nedhlss)
Similar variants
- CACNA1C p.Pro2000Ser Likely benign ★ same residue
- CACNA1C p.Pro2000_Gly2003del Uncertain significance ★★ same residue
- CACNA1C p.Pro2000_Gly2002del 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
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-pro2000 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown