Is CHRM5 p.Leu50Phe (c.150G>C) pathogenic?

CHRM5 p.Leu50Phe (c.150G>C) is classified Uncertain significance in CHRM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). AlphaMissense: likely pathogenic (0.6812); Very rare (popmax 0.00446%, eas).

How common is CHRM5 p.Leu50Phe (c.150G>C) in the general population?

CHRM5 p.Leu50Phe (c.150G>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CHRM5 p.Leu50Phe (c.150G>C)?

AlphaMissense predicts likely pathogenic (score 0.6812) — an in-silico prediction, not a clinical call.

CHRM5 p.Leu50Phe

c.150G>C · VCV3267144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.6812	likely pathogenic
REVEL	0.53	indeterminate
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.8	GERP -1.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,595 bp · p 9.6e-08 · regional, not allelic
Overall
CADD	20.1	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 0.00446% East Asian · 2/44,880 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000681% 11/1,614,166 alleles · very rare exomes 10/1,461,894 · genomes 1/152,272 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,945
East Asiangrpmax	0.00446%	22,440

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CHRM5
Protein: p.Leu50Phe
Coding: c.150G>C
MANE Select: NM_012125
Type: single nucleotide variant
Location: chr15:34062867 (GRCh38)

Full CHRM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/chrm5-p-leu50phe (accessed [today's date]).

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