Is CALM3 c.178+3G>A pathogenic?

CALM3 c.178+3G>A is classified Uncertain significance in CALM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-18). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CALM3 c.178+3G>A?

CALM3 c.178+3G>A is associated with Cardiovascular phenotype (ClinVar).

How common is CALM3 c.178+3G>A in the general population?

CALM3 c.178+3G>A is absent from gnomAD v4.1 (gnomAD).

CALM3 c.178+3G>A

rs1971787351 · VCV1779976

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.
Splicing
Splice region	donor +3	donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.70 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.7	GERP -3.1, phastCons 1
Non-coding constraint	Z 5.46	1 kb window · o/e 0.58 · regional · uncalibrated
Overall
CADD	18.15	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: CALM3
Coding: c.178+3G>A
MANE Select: NM_005184
dbSNP: rs1971787351
Type: single nucleotide variant
Location: chr19:46608343 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.93 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 85.45 · 26 PDB

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-c-178-plus-3g-a (accessed [today's date]).

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