Is CACNB2 p.Ser598= (c.1794T>C) pathogenic?

CACNB2 p.Ser598= (c.1794T>C) is classified Benign/Likely benign in CACNB2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.53%, sas); Associated with Brugada syndrome 4.

What condition is associated with CACNB2 p.Ser598= (c.1794T>C)?

CACNB2 p.Ser598= (c.1794T>C) is associated with Brugada syndrome 4 (ClinVar).

How common is CACNB2 p.Ser598= (c.1794T>C) in the general population?

CACNB2 p.Ser598= (c.1794T>C) is low-frequency (popmax 3.53%, sas) (gnomAD).

How is Brugada syndrome inherited?

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

CACNB2 p.Ser598=

c.1794T>C · rs34503140 · VCV299566

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.53%, sas)

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 -5.5	GERP -2.1
Overall
CADD	1.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.53% South Asian · 3,214/91,010 alleles

Filtering AF 3.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.39%

Overall 0.399% 6,434/1,613,426 alleles · low-frequency exomes 5,143/1,461,834 · genomes 1,291/151,592 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	3.53%	28
African / African-American	2.35%	43
East Asian	1.05%	95
Remaining individualsnot grpmax-eligible	0.47%	213
Finnishnot grpmax-eligible	0.442%	226
Middle Eastern	0.346%	289
Admixed American	0.204%	491
European (non-Finnish)	0.0231%	4,322
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800

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.Ser598=
Coding: c.1794T>C
MANE Select: NM_201596
dbSNP: rs34503140
Type: single nucleotide variant
Location: chr10:18539535 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 598: the 'disordered' region

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.Ser598Thr 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-ser598 (accessed [today's date]).

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