Is CACNB2 p.Asp573= (c.1719T>C) pathogenic?

CACNB2 p.Asp573= (c.1719T>C) is classified Likely benign in CACNB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). Very rare (popmax 0.00831%, nfe); Associated with Brugada syndrome 4.

What condition is associated with CACNB2 p.Asp573= (c.1719T>C)?

CACNB2 p.Asp573= (c.1719T>C) is associated with Brugada syndrome 4 (ClinVar).

How common is CACNB2 p.Asp573= (c.1719T>C) in the general population?

CACNB2 p.Asp573= (c.1719T>C) is very rare (popmax 0.00831%, 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.Asp573=

c.1719T>C · rs781283574 · VCV299565

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00831%, 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 -1	GERP -3.9, phastCons 0.004
Overall
CADD	1.592	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00831% European (non-Finnish) · 98/1,179,892 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00651% 105/1,613,414 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
European (non-Finnish)grpmax	0.00831%	12,040
Finnishnot grpmax-eligible	0.00469%	21,323
South Asian	0.0011%	91,016

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp573=
Coding: c.1719T>C
MANE Select: NM_201596
dbSNP: rs781283574
Type: single nucleotide variant
Location: chr10:18539460 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 573: 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.Asp573Ala Uncertain significance ★ ⚠ same residue
CACNB2 p.Asp573Gly 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

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-asp573 (accessed [today's date]).

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