Is CHRM3 p.Pro384= (c.1152C>T) pathogenic?

CHRM3 p.Pro384= (c.1152C>T) is classified Likely benign in CHRM3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-17). Rare (popmax 0.182%, mid); Associated with prune belly syndrome.

What condition is associated with CHRM3 p.Pro384= (c.1152C>T)?

CHRM3 p.Pro384= (c.1152C>T) is associated with prune belly syndrome (ClinVar).

How common is CHRM3 p.Pro384= (c.1152C>T) in the general population?

CHRM3 p.Pro384= (c.1152C>T) is rare (popmax 0.182%, mid) (gnomAD).

CHRM3 p.Pro384=

c.1152C>T · rs139780487 · VCV773822

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.182%, mid)

Conditions

prune belly syndrome

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 -0.15	GERP -0.84, phastCons 0.35
Overall
CADD	5.445	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.182% Middle Eastern · 11/6,034 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.079%

Overall 0.0206% 331/1,604,496 alleles · rare exomes 288/1,452,210 · genomes 43/152,286 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.182%	549
Ashkenazi Jewishnot grpmax-eligible	0.117%	857
Admixed American	0.0767%	1,304
Remaining individualsnot grpmax-eligible	0.0563%	1,777
African / African-American	0.0254%	3,942
European (non-Finnish)	0.0159%	6,286

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: CHRM3
Protein: p.Pro384=
Coding: c.1152C>T
MANE Select: NM_001375978
dbSNP: rs139780487
Type: single nucleotide variant
Location: chr1:239908603 (GRCh38)
Gene constraint: LOEUF 0.42 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 67.30 · 5 PDB

Full CHRM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

prune belly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRM3 p.Ala585Thr Uncertain significance ★★ ⚠ same condition
CHRM3 p.Ala589Asp Uncertain significance ★★ ⚠ same condition
CHRM3 p.Arg310His Uncertain significance ★★ ⚠ same condition
CHRM3 p.Arg44Gln Uncertain significance ★★ ⚠ same condition
CHRM3 p.Arg569Cys Uncertain significance ★★ ⚠ same condition
CHRM3 p.Arg584His Uncertain significance ★★ ⚠ same condition
CHRM3 p.Asn444Thr Uncertain significance ★★ ⚠ same condition
CHRM3 p.Gln430His 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/chrm3-p-pro384 (accessed [today's date]).

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