Is CHRM3 p.Ser299= (c.897C>T) pathogenic?

CHRM3 p.Ser299= (c.897C>T) is classified Likely benign in CHRM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-20). Rare (popmax 0.157%, sas).

How common is CHRM3 p.Ser299= (c.897C>T) in the general population?

CHRM3 p.Ser299= (c.897C>T) is rare (popmax 0.157%, sas) (gnomAD).

CHRM3 p.Ser299=

c.897C>T · rs147784522 · VCV2715031

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.157%, sas)

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 0.12	GERP 1.2, phastCons 0.012
Overall
CADD	6.587	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.157% South Asian · 143/91,086 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.0172% 278/1,614,114 alleles · rare exomes 260/1,461,840 · genomes 18/152,274 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.157%	637
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.016%	6,251
European (non-Finnish)	0.0103%	9,672

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.Ser299=
Coding: c.897C>T
MANE Select: NM_001375978
dbSNP: rs147784522
Type: single nucleotide variant
Location: chr1:239908348 (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.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
CHRM3 p.Asn444Thr 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-ser299 (accessed [today's date]).

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