Is CACNB2 p.Val164= (c.492A>G) pathogenic?

CACNB2 p.Val164= (c.492A>G) is classified Likely benign in CACNB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-23). Very rare (popmax 0.00356%, nfe); Associated with Brugada syndrome 4.

What condition is associated with CACNB2 p.Val164= (c.492A>G)?

CACNB2 p.Val164= (c.492A>G) is associated with Brugada syndrome 4 (ClinVar).

How common is CACNB2 p.Val164= (c.492A>G) in the general population?

CACNB2 p.Val164= (c.492A>G) is very rare (popmax 0.00356%, nfe) (gnomAD).

How is Brugada syndrome inherited?

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

CACNB2 p.Val164=

c.492A>G · rs748311933 · VCV1156527

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00356%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -3.9, phastCons 0.082
Overall
CADD	0.619	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00356% European (non-Finnish) · 42/1,179,882 alleles

Filtering AF 0.00267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00266% 43/1,613,868 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00356%	28,092
African / African-American	0.00133%	74,922

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.Val164=
Coding: c.492A>G
MANE Select: NM_201596
dbSNP: rs748311933
Type: single nucleotide variant
Location: chr10:18500847 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 164: the sh3 domain

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 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-val164 (accessed [today's date]).

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