CACNB2 p.Pro221=
c.663A>G · rs1213446253 · VCV702705
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000522%, nfe)
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 -0.16 | GERP -3.9, phastCons 0.002 |
| Overall | ||
| CADD | 4.161 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000522%
European (non-Finnish) · 6/1,149,272 alleles
Filtering AF
0.000188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000123%
Overall
0.00038%
6/1,580,040 alleles · very rare
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.Pro221=
- Coding
- c.663A>G
- MANE Select
- NM_201596
- dbSNP
- rs1213446253
- Type
- single nucleotide variant
- Location
- chr10:18506540 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.78 · 3 PDB
- Residue 221
- the 'disordered' region
Similar variants
- 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
- CACNB2 p.Ala229Asp 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-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown