Is CALM2 p.Pro44Arg (c.131C>G) pathogenic?

CALM2 p.Pro44Arg (c.131C>G) is classified Uncertain significance in CALM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CALM2 p.Pro44Arg (c.131C>G)?

CALM2 p.Pro44Arg (c.131C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is CALM2 p.Pro44Arg (c.131C>G) in the general population?

CALM2 p.Pro44Arg (c.131C>G) is absent from gnomAD v4.1 (gnomAD).

CALM2 p.Pro44Arg

c.131C>G · rs2465709286 · VCV3221772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
REVEL	0.901	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 16 kb · p 6.7e-26 · regional, not allelic
Overall
CADD	29.5	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: CALM2
Protein: p.Pro44Arg
Coding: c.131C>G
MANE Select: NM_001743
dbSNP: rs2465709286
Type: single nucleotide variant
Location: chr2:47162566 (GRCh38)
Gene constraint: LOEUF 0.262 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.82 · 21 PDB
Residue 44: the ef-hand 2 domain; an α-helix

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

Similar variants

CALM2 p.Pro44Ser Uncertain significance ★ same residue
CALM2 p.Asn98Ser Pathogenic ★★ same condition
CALM2 c.-2G>C Uncertain significance ★★ same condition
CALM2 c.-4C>T Uncertain significance ★★ same condition
CALM2 p.Arg107Cys Uncertain significance ★★ same condition
CALM2 p.Glu140= Uncertain significance ★★ same condition
CALM2 p.Val36Ile Uncertain significance ★★ same condition
CALM2 p.Asp81= 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/calm2-p-pro44arg (accessed [today's date]).

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