CACNB2 p.Arg547=
c.1641C>T · rs747741084 · VCV1773506
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
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 -0.015 | GERP -2.3, phastCons 0.027 |
| Overall | ||
| CADD | 7.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,008 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00137%
20/1,461,860 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,501 |
| South Asian | 0.0022% | 45,539 |
| European (non-Finnish) | 0.000847% | 118,002 |
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.Arg547=
- Coding
- c.1641C>T
- MANE Select
- NM_201596
- dbSNP
- rs747741084
- Type
- single nucleotide variant
- Location
- chr10:18539382 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.78 · 3 PDB
- Residue 547
- the 'disordered' region
Similar variants
- CACNB2 p.Arg547His Likely benign ★★ same residue
- CACNB2 p.Arg547Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- CACNB2 p.Arg547Ser Uncertain significance ★ ⚠ 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
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-arg547 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown