CACNB2 p.Arg608=
c.1824T>C · VCV4841440
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00268%, afr)
Conditions
1
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 -6 | GERP -3.9 |
| Overall | ||
| CADD | 0.078 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00268%
African / African-American · 2/74,540 alleles
Filtering AF
0.000445%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000167%
Overall
0.00031%
5/1,613,044 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00268% | 37,270 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 0.00017% | 589,946 |
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.Arg608=
- Coding
- c.1824T>C
- MANE Select
- NM_201596
- Type
- single nucleotide variant
- Location
- chr10:18539565 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.78 · 3 PDB
- Residue 608
- the 'disordered' region
Similar variants
- CACNB2 p.Arg608Cys Uncertain significance ★★ ⚠ same residue
- CACNB2 p.Arg608His Uncertain significance ★★ ⚠ same residue
- CACNB2 p.Arg608Leu Uncertain significance ★★ ⚠ same residue
- CACNB2 p.Arg608Gly Likely benign ★ same residue
- CACNB2 c.1206+5G>A Uncertain significance ★★ same condition
- CACNB2 c.1303-3C>T 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-arg608 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown