Is CHRM2 p.Thr15Lys (c.44C>A) pathogenic?

CHRM2 p.Thr15Lys (c.44C>A) is classified Uncertain significance in CHRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-04). AlphaMissense: likely benign (0.0815); Absent from gnomAD v4.1.

How common is CHRM2 p.Thr15Lys (c.44C>A) in the general population?

CHRM2 p.Thr15Lys (c.44C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRM2 p.Thr15Lys (c.44C>A)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

CHRM2 p.Thr15Lys

c.44C>A · rs1805069679 · VCV941681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -8.88	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 0.62	GERP -3, phastCons 0.97
Regional constraint	o/e 0.69	unconstrained · MANE · 314 bp · p 0.0005 · regional, not allelic
Overall
CADD	10.18	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHRM2
Protein: p.Thr15Lys
Coding: c.44C>A
MANE Select: NM_001006630
dbSNP: rs1805069679
Type: single nucleotide variant
Location: chr7:137014909 (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-thr15lys (accessed [today's date]).

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