Is CHRM2 p.Ser213= (c.639C>T) pathogenic?

CHRM2 p.Ser213= (c.639C>T) is classified Likely benign in CHRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). Very rare (popmax 0.00895%, eas).

How common is CHRM2 p.Ser213= (c.639C>T) in the general population?

CHRM2 p.Ser213= (c.639C>T) is very rare (popmax 0.00895%, eas) (gnomAD).

CHRM2 p.Ser213=

c.639C>T · rs753168342 · VCV2970663

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00895%, 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 1.2	GERP -1.9, phastCons 1
Overall
CADD	9.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00895% East Asian · 4/44,698 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.000274% 4/1,461,152 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.Ser213=
Coding: c.639C>T
MANE Select: NM_001006630
dbSNP: rs753168342
Type: single nucleotide variant
Location: chr7:137015504 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 72.87 · 17 PDB
Residue 213: an α-helix

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

Similar variants

CHRM2 p.Ser213Arg Uncertain significance ★ ⚠ same residue
CHRM2 p.Ser213Asn 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
CHRM2 p.Gly254Val 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-ser213 (accessed [today's date]).

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