Is CACNB2 p.Pro114= (c.342C>T) pathogenic?

CACNB2 p.Pro114= (c.342C>T) is classified Benign/Likely benign in CACNB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-17). Very rare (popmax 0.00407%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with CACNB2 p.Pro114= (c.342C>T)?

CACNB2 p.Pro114= (c.342C>T) is associated with Cardiovascular phenotype, Brugada syndrome 4 (ClinVar).

How common is CACNB2 p.Pro114= (c.342C>T) in the general population?

CACNB2 p.Pro114= (c.342C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

CACNB2 p.Pro114=

c.342C>T · rs368505003 · VCV537377

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

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 -6.5	GERP -3.9
Overall
CADD	1.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,179,998 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00328% 53/1,613,934 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,583
Admixed American	0.00333%	29,995
South Asian	0.0022%	45,536
Finnishnot grpmax-eligible	0.00156%	64,016

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.Pro114=
Coding: c.342C>T
MANE Select: NM_201596
dbSNP: rs368505003
Type: single nucleotide variant
Location: chr10:18498363 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 114: 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.Pro114Ala Uncertain significance ★★ ⚠ same residue
CACNB2 p.Pro114Ser Uncertain significance ★★ ⚠ same residue
CACNB2 p.Pro114Leu 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

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-pro114 (accessed [today's date]).

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