Is CASQ2 p.Lys40= (c.120G>A) pathogenic?

CASQ2 p.Lys40= (c.120G>A) is classified Likely benign in CASQ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-21). Absent from gnomAD v4.1; Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with CASQ2 p.Lys40= (c.120G>A)?

CASQ2 p.Lys40= (c.120G>A) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is CASQ2 p.Lys40= (c.120G>A) in the general population?

CASQ2 p.Lys40= (c.120G>A) is absent from gnomAD v4.1 (gnomAD).

CASQ2 p.Lys40=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.120G>A · VCV3623148

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

catecholaminergic polymorphic ventricular tachycardia 1

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 4	GERP 0.98, phastCons 1
Overall
CADD	15.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CASQ2
Protein: p.Lys40=
Coding: c.120G>A
MANE Select: NM_001232
Type: single nucleotide variant
Location: chr1:115768422 (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 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

CASQ2 p.Lys40Glu Uncertain significance ★★ ⚠ same residue
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.606+1G>C Pathogenic/Likely pathogenic ★★ same condition
CASQ2 c.606+2T>A Likely pathogenic ★★ same condition
CASQ2 c.737+1G>A Pathogenic/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-lys40 (accessed [today's date]).

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