CACNB2 p.Arg120Gln
c.359G>A · rs202220375 · VCV191431
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6403 | likely pathogenic |
|---|---|---|
| REVEL | 0.702 | pathogenic-leaning |
| SaProt | LLR -13.15 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2, phastCons 1 |
| Regional constraint | o/e 1.10 | unconstrained · MANE · 399 kb · p 0.0029 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,020 |
| European (non-Finnish) | 8.47e-05% | 1,179,994 |
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.Arg120Gln
- Coding
- c.359G>A
- MANE Select
- NM_201596
- dbSNP
- rs202220375
- Type
- single nucleotide variant
- Location
- chr10:18498380 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.78 · 3 PDB
- Residue 120
- the sh3 domain
Disease context
Brugada syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Brugada syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Not applicable
- Onset
- Adult, Childhood
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- CACNB2 p.Arg120= Likely benign ★★ same residue
- CACNB2 p.Arg120Trp 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
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-arg120gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown