Is CALM1 p.Lys78= (c.234A>G) pathogenic?

CALM1 p.Lys78= (c.234A>G) is classified Likely benign in CALM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-16). Ultra-rare (popmax 0.0329%, sas); Associated with Cardiovascular phenotype.

What condition is associated with CALM1 p.Lys78= (c.234A>G)?

CALM1 p.Lys78= (c.234A>G) is associated with Cardiovascular phenotype, catecholaminergic polymorphic ventricular tachycardia 4, long QT syndrome 14 (ClinVar).

How common is CALM1 p.Lys78= (c.234A>G) in the general population?

CALM1 p.Lys78= (c.234A>G) is ultra-rare (popmax 0.0329%, sas) (gnomAD).

CALM1 p.Lys78=

c.234A>G · rs556733562 · VCV2158816

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, sas)

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 4.7	GERP 0.63, phastCons 1
Overall
CADD	10.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% South Asian · 30/91,064 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00198% 32/1,613,716 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0329%	3,035
Remaining individualsnot grpmax-eligible	0.0032%	31,241

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: CALM1
Protein: p.Lys78=
Coding: c.234A>G
MANE Select: NM_006888
dbSNP: rs556733562
Type: single nucleotide variant
Location: chr14:90403917 (GRCh38)
Gene constraint: LOEUF 0.276 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.22 · 351 PDB
Residue 78: the ef-hand 2 domain; 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.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
CALM1 c.285+15A>G 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-lys78 (accessed [today's date]).

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