CACNB2 p.Ala352=
c.1056G>A · rs730880058 · VCV180289
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.87 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.52 | gain · loss 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.39 | GERP -3.9, phastCons 0.007 |
| Overall | ||
| CADD | 21.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,872 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00155%
25/1,613,800 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,872 |
| European (non-Finnish) | 0.00186% | 53,633 |
| Finnishnot grpmax-eligible | 0.00156% | 63,984 |
| African / African-American | 0.00134% | 74,876 |
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
- CACNB2
- Protein
- p.Ala352=
- Coding
- c.1056G>A
- MANE Select
- NM_201596
- dbSNP
- rs730880058
- Type
- single nucleotide variant
- Location
- chr10:18534077 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.78 · 3 PDB
Similar variants
- CACNB2 p.Ala352Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- CACNB2 c.1206+5G>A Uncertain significance ★★ same condition
- CACNB2 c.1303-3C>T Uncertain significance ★★ same condition
- CACNB2 c.1488+6G>A Uncertain significance ★★ same condition
- CACNB2 p.Ala105Thr Uncertain significance ★★ ⚠ same condition
- CACNB2 p.Ala118Val Uncertain significance ★★ ⚠ same condition
- CACNB2 p.Ala128Val Uncertain significance ★★ ⚠ same condition
- CACNB2 p.Ala139Ser Uncertain significance ★★ ⚠ 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/cacnb2-p-ala352 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown