Is CALM3 p.Val137= (c.411C>T) pathogenic?

CALM3 p.Val137= (c.411C>T) is classified Likely benign in CALM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-27). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CALM3 p.Val137= (c.411C>T)?

CALM3 p.Val137= (c.411C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is CALM3 p.Val137= (c.411C>T) in the general population?

CALM3 p.Val137= (c.411C>T) is absent from gnomAD v4.1 (gnomAD).

CALM3 p.Val137=

c.411C>T · rs1599759588 · VCV2625025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,754)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.95 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP -2.4, phastCons 1
Overall
CADD	13.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,602,754). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CALM3
Protein: p.Val137=
Coding: c.411C>T
MANE Select: NM_005184
dbSNP: rs1599759588
Type: single nucleotide variant
Location: chr19:46608971 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.93 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 26 PDB
Residue 137: the ef-hand 4 domain; a β-strand; the 'necessary and sufficient for interaction with pcp4' region

Full CALM3 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

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.Asp132Asn Uncertain significance ★★ ⚠ same condition
CALM3 p.Gly135Asp Uncertain significance ★★ ⚠ same condition
CALM3 p.Gly26Asp Uncertain significance ★★ ⚠ same condition
CALM3 p.Ala103= Likely benign ★★ same condition
CALM3 p.Ala148= 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/calm3-p-val137 (accessed [today's date]).

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