Is CACNB2 p.Pro433Val (c.1297_1298delinsGT) pathogenic?

CACNB2 p.Pro433Val (c.12971298delinsGT) is classified Uncertain significance in CACNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). No gnomAD frequency available for this variant; Associated with Brugada syndrome 4.

What condition is associated with CACNB2 p.Pro433Val (c.1297_1298delinsGT)?

CACNB2 p.Pro433Val (c.1297_1298delinsGT) is associated with Brugada syndrome 4 (ClinVar).

How common is CACNB2 p.Pro433Val (c.1297_1298delinsGT) in the general population?

CACNB2 p.Pro433Val (c.1297_1298delinsGT) is no gnomAD frequency available for this variant (gnomAD).

How is Brugada syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CACNB2 p.Pro433Val

c.1297_1298delinsGT · rs2494820204 · VCV2011379

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Brugada syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 399 kb · p 0.0029 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CACNB2
Protein: p.Pro433Val
Coding: c.1297_1298delinsGT
MANE Select: NM_201596
dbSNP: rs2494820204
Type: Indel
Location: chr10:18536191 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB

Full CACNB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Brugada syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Brugada syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CACNB2 p.Pro433Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
CACNB2 p.Arg506His Uncertain significance ★★ same condition
CACNB2 c.1489-17_1489-16delinsTT Uncertain significance ★ same condition
CACNB2 p.Pro433= Likely benign ★ 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 c.944+3_944+6del 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-pro433val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown