Is CASQ2 p.Asp350= (c.1050C>T) pathogenic?

CASQ2 p.Asp350= (c.1050C>T) is classified Likely benign in CASQ2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-03). Very rare (popmax 0.00534%, afr); Associated with catecholaminergic polymorphic ventricular tachycardia 2.

What condition is associated with CASQ2 p.Asp350= (c.1050C>T)?

CASQ2 p.Asp350= (c.1050C>T) is associated with catecholaminergic polymorphic ventricular tachycardia 2, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is CASQ2 p.Asp350= (c.1050C>T) in the general population?

CASQ2 p.Asp350= (c.1050C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

CASQ2 p.Asp350=

Q: How is Catecholaminergic polymorphic ventricular tachycardia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1050C>T · rs758060229 · VCV1596743

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

catecholaminergic polymorphic ventricular tachycardia 2

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 -8	GERP -5.6
Overall
CADD	0.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,864 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0013% 21/1,613,566 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,716
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,880
European (non-Finnish)	0.00119%	84,263
South Asian	0.0011%	91,064

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: CASQ2
Protein: p.Asp350=
Coding: c.1050C>T
MANE Select: NM_001232
dbSNP: rs758060229
Type: single nucleotide variant
Location: chr1:115701391 (GRCh38)
Gene constraint: LOEUF 1.322 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.63 · 4 PDB

Full CASQ2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

catecholaminergic polymorphic ventricular tachycardia 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: catecholaminergic polymorphic ventricular tachycardia 1

For Catecholaminergic polymorphic ventricular tachycardia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CASQ2 c.235-2A>G Likely pathogenic ★★ same condition
CASQ2 c.319+2T>G Likely pathogenic ★★ same condition
CASQ2 c.320-2A>G Pathogenic ★★ same condition
CASQ2 c.420+1G>A Likely pathogenic ★★ same condition
CASQ2 c.532+1G>A Pathogenic/Likely pathogenic ★★ same condition
CASQ2 c.533-2A>G Likely pathogenic ★★ same condition
CASQ2 c.606+1G>C Pathogenic/Likely pathogenic ★★ same condition
CASQ2 c.606+2T>A Likely pathogenic ★★ 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/casq2-p-asp350 (accessed [today's date]).

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