Is CHRM3 p.Pro372= (c.1116G>A) pathogenic?

CHRM3 p.Pro372= (c.1116G>A) is classified Likely benign in CHRM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). Ultra-rare (popmax 0.052%, eas).

How common is CHRM3 p.Pro372= (c.1116G>A) in the general population?

CHRM3 p.Pro372= (c.1116G>A) is ultra-rare (popmax 0.052%, eas) (gnomAD).

CHRM3 p.Pro372=

c.1116G>A · rs138859152 · VCV1925404

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, eas)

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 -9.9	GERP -4.2
Overall
CADD	0.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.052% East Asian · 23/44,258 alleles

Filtering AF 0.0355% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.03%

Overall 0.00289% 46/1,589,614 alleles · ultra-rare exomes 38/1,437,434 · genomes 8/152,180 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.052%	1,924
Admixed American	0.00701%	14,259
African / African-American	0.00403%	24,823
European (non-Finnish)	0.00128%	77,868
South Asian	0.00115%	86,910

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.Pro372=
Coding: c.1116G>A
MANE Select: NM_001375978
dbSNP: rs138859152
Type: single nucleotide variant
Location: chr1:239908567 (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

Similar variants

CHRM3 p.Pro372Leu Uncertain significance ★ ⚠ same residue
CHRM3 p.Ala585Thr Uncertain significance ★★ ⚠ same type
CHRM3 p.Ala589Asp Uncertain significance ★★ ⚠ same type
CHRM3 p.Arg310His Uncertain significance ★★ ⚠ same type
CHRM3 p.Arg44Gln Uncertain significance ★★ ⚠ same type
CHRM3 p.Arg569Cys Uncertain significance ★★ ⚠ same type
CHRM3 p.Arg584His Uncertain significance ★★ ⚠ same type
CHRM3 p.Asn339Lys Uncertain significance ★★ ⚠ same type

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-pro372 (accessed [today's date]).

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