Is CALM3 p.Thr71= (c.213C>T) pathogenic?

CALM3 p.Thr71= (c.213C>T) is classified Likely benign in CALM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-09). Ultra-rare (popmax 0.0165%, mid); Associated with long QT syndrome 1.

What condition is associated with CALM3 p.Thr71= (c.213C>T)?

CALM3 p.Thr71= (c.213C>T) is associated with long QT syndrome 1 (ClinVar).

How common is CALM3 p.Thr71= (c.213C>T) in the general population?

CALM3 p.Thr71= (c.213C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Romano-Ward syndrome inherited?

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

CALM3 p.Thr71=

c.213C>T · rs1568666350 · VCV2795402

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

long QT syndrome 1

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 0.8	GERP -3.7, phastCons 1
Overall
CADD	12.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.84e-05% 1/1,461,840 alleles · ultra-rare

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: CALM3
Protein: p.Thr71=
Coding: c.213C>T
MANE Select: NM_005184
dbSNP: rs1568666350
Type: single nucleotide variant
Location: chr19:46608516 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.93 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 26 PDB
Residue 71: the ef-hand 2 domain; an α-helix

Full CALM3 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

CALM3 p.Asp94Ala Pathogenic/Likely pathogenic ★★ same condition
CALM3 p.Asp96His Pathogenic/Likely pathogenic ★★ same condition
CALM3 p.Glu141Lys Pathogenic ★★ same condition
CALM3 c.34+3G>A Uncertain significance ★★ same condition
CALM3 c.421+5G>A Uncertain significance ★★ same condition
CALM3 p.Ala148Thr Uncertain significance ★★ ⚠ same condition
CALM3 p.Arg107Cys Uncertain significance ★★ ⚠ same condition
CALM3 p.Asp132Asn 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/calm3-p-thr71 (accessed [today's date]).

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