Is CASQ2 p.Asp307= (c.921C>T) pathogenic?

CASQ2 p.Asp307= (c.921C>T) is classified Likely benign in CASQ2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-23). Very rare (popmax 8.48e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with CASQ2 p.Asp307= (c.921C>T)?

CASQ2 p.Asp307= (c.921C>T) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 1 (ClinVar).

How common is CASQ2 p.Asp307= (c.921C>T) in the general population?

CASQ2 p.Asp307= (c.921C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CASQ2 p.Asp307=

c.921C>T · rs773111521 · VCV415253

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 4.1	GERP 1.6, phastCons 1
Overall
CADD	9.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,850 alleles

Overall 6.85e-05% 1/1,460,590 alleles · very rare

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.Asp307=
Coding: c.921C>T
MANE Select: NM_001232
dbSNP: rs773111521
Type: single nucleotide variant
Location: chr1:115705210 (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 307: a UniProt-annotated variant site (in cpvt2; reduces calcium-binding; impairs calcium-dependent oligomerization; causes 50% decrease in calcium-dependent binding to trdn; causes 50% decrease in calcium-dependent binding to asph)

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

Similar variants

CASQ2 p.Asp307Asn Uncertain significance ★ ⚠ same residue
CASQ2 p.Asp307Glu Uncertain significance ★ ⚠ same residue
CASQ2 p.Asp307His Pathogenic 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.533-2A>G 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-asp307 (accessed [today's date]).

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