Is CHRM2 p.Pro372Ala (c.1114C>G) pathogenic?

CHRM2 p.Pro372Ala (c.1114C>G) is classified Likely benign in CHRM2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.1273); Rare (popmax 0.119%, nfe).

How common is CHRM2 p.Pro372Ala (c.1114C>G) in the general population?

CHRM2 p.Pro372Ala (c.1114C>G) is rare (popmax 0.119%, nfe) (gnomAD).

What do computational predictors say about CHRM2 p.Pro372Ala (c.1114C>G)?

AlphaMissense predicts likely benign (score 0.1273) — an in-silico prediction, not a clinical call.

CHRM2 p.Pro372Ala

c.1114C>G · rs138806839 · VCV227247

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1273 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1273	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 646 bp · p 0.96 · regional, not allelic
Overall
CADD	19.65	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.119% European (non-Finnish) · 1,403/1,179,426 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.102% 1,641/1,613,088 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.267%	374
European (non-Finnish)grpmax	0.119%	841
Remaining individualsnot grpmax-eligible	0.0769%	1,301
Admixed American	0.015%	6,656
African / African-American	0.0107%	9,368
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,582
South Asian	0.0011%	91,040

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CHRM2
Protein: p.Pro372Ala
Coding: c.1114C>G
MANE Select: NM_001006630
dbSNP: rs138806839
Type: single nucleotide variant
Location: chr7:137015979 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 72.87 · 17 PDB

Full CHRM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRM2 p.Ala265Val Uncertain significance ★★ ⚠ same type
CHRM2 p.Arg52Cys Uncertain significance ★★ ⚠ same type
CHRM2 p.Gln358His Uncertain significance ★★ ⚠ same type
CHRM2 p.Glu305Gly Uncertain significance ★★ ⚠ same type
CHRM2 p.Gly238Ala Uncertain significance ★★ ⚠ same type
CHRM2 p.Gly254Val Uncertain significance ★★ ⚠ same type
CHRM2 p.Gly277Glu Uncertain significance ★★ ⚠ same type
CHRM2 p.Ile325Phe 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/chrm2-p-pro372ala (accessed [today's date]).

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