Is CHRM2 p.Arg381= (c.1143G>T) pathogenic?

CHRM2 p.Arg381= (c.1143G>T) is classified Likely benign in CHRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Very rare (popmax 0.00134%, afr).

How common is CHRM2 p.Arg381= (c.1143G>T) in the general population?

CHRM2 p.Arg381= (c.1143G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

CHRM2 p.Arg381=

c.1143G>T · rs1227972027 · VCV1150146

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 1.5	GERP -1.7, phastCons 1
Overall
CADD	6.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,802 alleles

Overall 0.000658% 1/151,876 alleles · very rare

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.Arg381=
Coding: c.1143G>T
MANE Select: NM_001006630
dbSNP: rs1227972027
Type: single nucleotide variant
Location: chr7:137016008 (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.Arg381Gln Uncertain significance ★ ⚠ same residue
CHRM2 p.Arg381Leu Uncertain significance ★ ⚠ same residue
CHRM2 p.Arg381Trp Uncertain significance ★ ⚠ same residue
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

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-arg381 (accessed [today's date]).

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