Is CACNB2 p.Arg406= (c.1216A>C) pathogenic?

CACNB2 p.Arg406= (c.1216A>C) is classified Likely benign in CACNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CACNB2 p.Arg406= (c.1216A>C)?

CACNB2 p.Arg406= (c.1216A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is CACNB2 p.Arg406= (c.1216A>C) in the general population?

CACNB2 p.Arg406= (c.1216A>C) is absent from gnomAD v4.1 (gnomAD).

CACNB2 p.Arg406=

c.1216A>C · rs2494818009 · VCV2625178

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 5.1	GERP -3.1, phastCons 1
Overall
CADD	8.771	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CACNB2
Protein: p.Arg406=
Coding: c.1216A>C
MANE Select: NM_201596
dbSNP: rs2494818009
Type: single nucleotide variant
Location: chr10:18536110 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 406: an α-helix

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

Similar variants

CACNB2 p.Arg406Ser Uncertain significance ★ ⚠ 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
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-arg406 (accessed [today's date]).

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