Is CACNB2 p.Arg162Gln (c.485G>A) pathogenic?

CACNB2 p.Arg162Gln (c.485G>A) is classified Uncertain significance in CACNB2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-04-25). AlphaMissense: likely pathogenic (0.9061); Very rare (popmax 0.00525%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with CACNB2 p.Arg162Gln (c.485G>A)?

CACNB2 p.Arg162Gln (c.485G>A) is associated with Cardiovascular phenotype, Brugada syndrome 4 (ClinVar).

How common is CACNB2 p.Arg162Gln (c.485G>A) in the general population?

CACNB2 p.Arg162Gln (c.485G>A) is very rare (popmax 0.00525%, nfe) (gnomAD).

What do computational predictors say about CACNB2 p.Arg162Gln (c.485G>A)?

AlphaMissense predicts likely pathogenic (score 0.9061) — an in-silico prediction, not a clinical call.

CACNB2 p.Arg162Gln

c.485G>A · rs144461906 · VCV469645

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9061 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9061	likely pathogenic
REVEL	0.714	pathogenic-leaning
SaProt	LLR -16.27	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 8.7	GERP 0.92, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 399 kb · p 0.0029 · regional, not allelic
Overall
CADD	25.4	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

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00525% European (non-Finnish) · 62/1,179,878 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00415% 67/1,613,794 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,030
East Asian	0.00223%	44,882
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00134%	74,902
South Asian	0.0011%	91,082

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.Arg162Gln
Coding: c.485G>A
MANE Select: NM_201596
dbSNP: rs144461906
Type: single nucleotide variant
Location: chr10:18500840 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 162: the sh3 domain

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Brugada syndrome 4

Similar variants

CACNB2 p.Arg162Leu 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
CACNB2 p.Ala128Val Uncertain significance ★★ ⚠ same condition
CACNB2 p.Ala139Ser 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-arg162gln (accessed [today's date]).

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