Is CHRM5 p.Pro191= (c.573C>T) pathogenic?

CHRM5 p.Pro191= (c.573C>T) is classified Benign in CHRM5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-18). Low-frequency (popmax 1.02%, afr).

How common is CHRM5 p.Pro191= (c.573C>T) in the general population?

CHRM5 p.Pro191= (c.573C>T) is low-frequency (popmax 1.02%, afr) (gnomAD).

CHRM5 p.Pro191=

c.573C>T · rs139101467 · VCV710292

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.02%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.095	GERP -2.4, phastCons 0.91
Overall
CADD	13.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.02% African / African-American · 766/75,022 alleles

Filtering AF 0.961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.937%

Overall 0.0515% 832/1,614,144 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.02%	98
Remaining individualsnot grpmax-eligible	0.048%	2,084
Admixed American	0.0417%	2,401
South Asian	0.0011%	91,078
European (non-Finnish)	0.000847%	118,003

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.Pro191=
Coding: c.573C>T
MANE Select: NM_020371 · reported on NM_012125
dbSNP: rs139101467
Type: single nucleotide variant
Location: chr15:34063290 (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-pro191 (accessed [today's date]).

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