Is CACNB2 p.Tyr567= (c.1701C>T) pathogenic?

CACNB2 p.Tyr567= (c.1701C>T) is classified Benign in CACNB2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 35.2%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with CACNB2 p.Tyr567= (c.1701C>T)?

CACNB2 p.Tyr567= (c.1701C>T) is associated with Cardiovascular phenotype, Brugada syndrome 4 (ClinVar).

CACNB2 p.Tyr567=

Q: How common is CACNB2 p.Tyr567= (c.1701C>T) in the general population?

CACNB2 p.Tyr567= (c.1701C>T) is common (popmax 35.2%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1701C>T · rs2228645 · VCV263261

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 35.2%, amr) — too common for a highly-penetrant pathogenic allele

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 -10	GERP -3.5
Overall
CADD	0.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.2% Admixed American · 21,079/59,936 alleles

Filtering AF 34.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 34.6%

Overall 18.2% 293,577/1,613,638 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	35.2%	3
South Asian	29.1%	3
East Asian	25.8%	4
African / African-American	19.8%	5
Finnishnot grpmax-eligible	19.1%	5
Remaining individualsnot grpmax-eligible	17.6%	6
European (non-Finnish)	16.2%	6
Ashkenazi Jewishnot grpmax-eligible	16%	6
Amishnot grpmax-eligible	15.6%	6
Middle Eastern	12.2%	8

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.Tyr567=
Coding: c.1701C>T
MANE Select: NM_201596
dbSNP: rs2228645
Type: single nucleotide variant
Location: chr10:18539442 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.78 · 3 PDB
Residue 567: the 'disordered' region

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.Tyr567Cys Uncertain significance ★ ⚠ same residue
CACNB2 p.Tyr567Ter 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-tyr567 (accessed [today's date]).

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