Is CHRM2 p.Phe152Val (c.454T>G) pathogenic?

CHRM2 p.Phe152Val (c.454T>G) is classified Uncertain significance in CHRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: likely pathogenic (0.6328); Absent from gnomAD v4.1.

How common is CHRM2 p.Phe152Val (c.454T>G) in the general population?

CHRM2 p.Phe152Val (c.454T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHRM2 p.Phe152Val (c.454T>G)?

AlphaMissense predicts likely pathogenic (score 0.6328) — an in-silico prediction, not a clinical call.

CHRM2 p.Phe152Val

c.454T>G · rs2131132038 · VCV1393722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6328 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6328	likely pathogenic
REVEL	0.413	indeterminate
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 133 bp · p 0.00013 · regional, not allelic
Overall
CADD	28.5	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

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.Phe152Val
Coding: c.454T>G
MANE Select: NM_001006630
dbSNP: rs2131132038
Type: single nucleotide variant
Location: chr7:137015319 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 72.87 · 17 PDB
Residue 152: a disulfide bond; an α-helix

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

Similar variants

CHRM2 p.Phe152= Benign ★★ 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
CHRM2 p.Gly277Glu 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-phe152val (accessed [today's date]).

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