Is CALM2 p.Glu83Lys (c.247G>A) pathogenic?

CALM2 p.Glu83Lys (c.247G>A) is classified Uncertain significance in CALM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-25). Absent from gnomAD v4.1; Associated with long QT syndrome 1.

What condition is associated with CALM2 p.Glu83Lys (c.247G>A)?

CALM2 p.Glu83Lys (c.247G>A) is associated with long QT syndrome 1 (ClinVar).

How common is CALM2 p.Glu83Lys (c.247G>A) in the general population?

CALM2 p.Glu83Lys (c.247G>A) is absent from gnomAD v4.1 (gnomAD).

How is Romano-Ward syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CALM2 p.Glu83Lys

c.247G>A · rs1687185703 · VCV854156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

long QT syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.827	moderately pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 16 kb · p 6.7e-26 · regional, not allelic
Overall
CADD	31.0	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.Glu83Lys
Coding: c.247G>A
MANE Select: NM_001743
dbSNP: rs1687185703
Type: single nucleotide variant
Location: chr2:47162324 (GRCh38)
Gene constraint: LOEUF 0.262 · pLI 0.99 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.82 · 21 PDB
Residue 83: the ef-hand 3 domain; an α-helix; 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

long QT syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Romano-Ward syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CALM2 p.Glu83= Likely benign ★ same residue
CALM2 p.Glu83Gly Uncertain significance ★ same residue
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 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-glu83lys (accessed [today's date]).

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