Is CALM2 p.Asp81= (c.243C>T) pathogenic?

CALM2 p.Asp81= (c.243C>T) is classified Benign/Likely benign in CALM2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-03-01). Rare (popmax 0.264%, mid); Associated with Cardiovascular phenotype.

What condition is associated with CALM2 p.Asp81= (c.243C>T)?

CALM2 p.Asp81= (c.243C>T) is associated with Cardiovascular phenotype, long QT syndrome 1 (ClinVar).

How common is CALM2 p.Asp81= (c.243C>T) in the general population?

CALM2 p.Asp81= (c.243C>T) is rare (popmax 0.264%, mid) (gnomAD).

CALM2 p.Asp81=

c.243C>T · rs141298844 · VCV239033

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.264%, mid)

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 1.9	GERP 1.3, phastCons 1
Overall
CADD	8.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.264% Middle Eastern · 16/6,056 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.135%

Overall 0.0742% 1,197/1,612,308 alleles · rare exomes 1,108/1,460,304 · genomes 89/152,004 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.264%	378
European (non-Finnish)	0.0851%	1,176
Remaining individualsnot grpmax-eligible	0.0833%	1,200
Ashkenazi Jewishnot grpmax-eligible	0.0677%	1,476
South Asian	0.055%	1,817
Admixed American	0.0485%	2,062
Finnishnot grpmax-eligible	0.0282%	3,549
African / African-American	0.012%	8,319

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: CALM2
Protein: p.Asp81=
Coding: c.243C>T
MANE Select: NM_001743
dbSNP: rs141298844
Type: single nucleotide variant
Location: chr2:47162328 (GRCh38)
Gene constraint: LOEUF 0.262 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.82 · 21 PDB
Residue 81: the ef-hand 3 domain; the 'necessary and sufficient for interaction with pcp4' region

Full CALM2 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: long QT syndrome 1

Similar variants

CALM2 p.Asn98Ser Pathogenic ★★ same condition
CALM2 p.Asp134Asn Likely pathogenic ★★ same condition
CALM2 p.Asp96Tyr Pathogenic/Likely pathogenic ★★ same condition
CALM2 p.Asp96Val Pathogenic ★★ same condition
CALM2 c.285+5G>A Uncertain significance ★★ same condition
CALM2 c.-2G>C Uncertain significance ★★ same condition
CALM2 c.-4C>T Uncertain significance ★★ same condition
CALM2 p.Ala58Pro Uncertain significance ★★ 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/calm2-p-asp81 (accessed [today's date]).

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