CACNA1C p.Ala1826Val
c.5477C>T · rs750289082 · VCV456981
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
long QT syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.249 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.014 | GERP -2.9, phastCons 0.81 |
| Regional constraint | o/e 0.84 | unconstrained · MANE · 14 kb · p 2.9e-05 · regional, not allelic |
| Overall | ||
| CADD | 4.603 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,056 alleles
Filtering AF
0.0043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00296%
Overall
0.00143%
23/1,611,978 alleles · ultra-rare
exomes 15/1,459,850 · genomes 8/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,056 |
| Admixed American | 0.01% | 9,969 |
| European (non-Finnish) | 0.00136% | 73,700 |
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.Ala1826Val
- Coding
- c.5477C>T
- MANE Select
- NM_000719
- dbSNP
- rs750289082
- Type
- single nucleotide variant
- Location
- chr12:2682582 (GRCh38)
- Gene constraint
- LOEUF 0.186 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.73 · 33 PDB
- Residue 1826
- a UniProt-annotated variant site (in nedhlss); the 'disordered' region
Similar variants
- CACNA1C p.Ala1826= Benign/Likely benign ★★ 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.Glu1115Lys Pathogenic/Likely pathogenic ★★ same condition
- CACNA1C p.Gly1378Arg 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-ala1826val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown