Is CALM1 p.Thr80= (c.240A>G) pathogenic?

CALM1 p.Thr80= (c.240A>G) is classified Likely benign in CALM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-28). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CALM1 p.Thr80= (c.240A>G)?

CALM1 p.Thr80= (c.240A>G) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 4, long QT syndrome 14 (ClinVar).

How common is CALM1 p.Thr80= (c.240A>G) in the general population?

CALM1 p.Thr80= (c.240A>G) is absent from gnomAD v4.1 (gnomAD).

CALM1 p.Thr80=

c.240A>G · VCV3751972

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.9	GERP -3.7, phastCons 0.98
Overall
CADD	9.295	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: CALM1
Protein: p.Thr80=
Coding: c.240A>G
MANE Select: NM_006888
Type: single nucleotide variant
Location: chr14:90403923 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.22 · 351 PDB
Residue 80: an α-helix; the 'necessary and sufficient for interaction with pcp4' region

Full CALM1 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 4 long QT syndrome 14

Similar variants

CALM1 p.Thr80_Asp81del Uncertain significance ★ same residue
CALM1 p.Asn98Ser Pathogenic/Likely pathogenic ★★ same condition
CALM1 p.Asp130Gly Pathogenic/Likely pathogenic ★★ same condition
CALM1 c.4-3T>C Uncertain significance ★★ same condition
CALM1 p.Arg87His Uncertain significance ★★ same condition
CALM1 p.Glu120Lys Uncertain significance ★★ same condition
CALM1 c.178+18A>G Benign/Likely benign ★★ same condition
CALM1 c.179-4C>T Benign/Likely benign ★★ 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/calm1-p-thr80 (accessed [today's date]).

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