Is CHRM2 p.Thr287Ser (c.860C>G) pathogenic?

CHRM2 p.Thr287Ser (c.860C>G) is classified Conflicting classifications of pathogenicity in CHRM2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-29). AlphaMissense: likely benign (0.1058); Rare (popmax 0.204%, afr).

How common is CHRM2 p.Thr287Ser (c.860C>G) in the general population?

CHRM2 p.Thr287Ser (c.860C>G) is rare (popmax 0.204%, afr) (gnomAD).

What do computational predictors say about CHRM2 p.Thr287Ser (c.860C>G)?

AlphaMissense predicts likely benign (score 0.1058) — an in-silico prediction, not a clinical call.

CHRM2 p.Thr287Ser

c.860C>G · rs138193709 · VCV228517

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1058 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.204%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1058	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.36	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 6	GERP 0.94, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 646 bp · p 0.96 · regional, not allelic
Overall
CADD	19.67	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 0.204% African / African-American · 153/74,962 alleles

Filtering AF 0.178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.168%

Overall 0.0101% 163/1,613,284 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.204%	490
Remaining individualsnot grpmax-eligible	0.0112%	8,924
Admixed American	0.00167%	59,908
South Asian	0.0011%	91,070
European (non-Finnish)	8.48e-05%	1,179,567

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.Thr287Ser
Coding: c.860C>G
MANE Select: NM_001006630
dbSNP: rs138193709
Type: single nucleotide variant
Location: chr7:137015725 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 72.87 · 17 PDB
Residue 287: the 'disordered' region

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-thr287ser (accessed [today's date]).

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