Is CASQ2 p.Pro279= (c.837A>T) pathogenic?

CASQ2 p.Pro279= (c.837A>T) is classified Uncertain significance in CASQ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-04). Absent from gnomAD v4.1; Associated with catecholaminergic polymorphic ventricular tachycardia 1.

What condition is associated with CASQ2 p.Pro279= (c.837A>T)?

CASQ2 p.Pro279= (c.837A>T) is associated with catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is CASQ2 p.Pro279= (c.837A>T) in the general population?

CASQ2 p.Pro279= (c.837A>T) is absent from gnomAD v4.1 (gnomAD).

CASQ2 p.Pro279=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.837A>T · rs1647217312 · VCV1001675

Uncertain significance Single submitter

Classification

Uncertain significance

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.38	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.23	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.5	GERP 0.27, phastCons 1
Overall
CADD	19.23	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.Pro279=
Coding: c.837A>T
MANE Select: NM_001232
dbSNP: rs1647217312
Type: single nucleotide variant
Location: chr1:115717841 (GRCh38)
Gene constraint: LOEUF 1.322 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.63 · 4 PDB
Residue 279: an α-helix

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.Pro279Thr 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-pro279 (accessed [today's date]).

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