Is CASQ2 p.Asp396= (c.1188T>C) pathogenic?

CASQ2 p.Asp396= (c.1188T>C) is classified Likely benign in CASQ2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-13). Very rare (popmax 0.00669%, eas); Associated with Cardiovascular phenotype.

How common is CASQ2 p.Asp396= (c.1188T>C) in the general population?

CASQ2 p.Asp396= (c.1188T>C) is very rare (popmax 0.00669%, eas) (gnomAD).

CASQ2 p.Asp396=

Q: What condition is associated with CASQ2 p.Asp396= (c.1188T>C)?

CASQ2 p.Asp396= (c.1188T>C) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1, catecholaminergic polymorphic ventricular tachycardia 2 (ClinVar).

c.1188T>C · rs751885773 · VCV238669

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

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 -4.2	GERP -3.7
Overall
CADD	0.894	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,846 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00124%

Overall 0.00224% 36/1,605,714 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,907
East Asiangrpmax	0.00669%	14,949
South Asian	0.0022%	45,386
European (non-Finnish)	0.00213%	46,917
Remaining individualsnot grpmax-eligible	0.00161%	62,212

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: CASQ2
Protein: p.Asp396=
Coding: c.1188T>C
MANE Select: NM_001232
dbSNP: rs751885773
Type: single nucleotide variant
Location: chr1:115701253 (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 396: the 'disordered' region

Full CASQ2 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: catecholaminergic polymorphic ventricular tachycardia 1 catecholaminergic polymorphic ventricular tachycardia 2

Similar variants

CASQ2 p.Asp396Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
CASQ2 p.Asp396Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
CASQ2 p.Asp396Val 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.532+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-asp396 (accessed [today's date]).

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