Is CHRM1 p.Arg454= (c.1362C>T) pathogenic?

CHRM1 p.Arg454= (c.1362C>T) is classified Likely benign in CHRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). Very rare (popmax 0.00266%, afr).

How common is CHRM1 p.Arg454= (c.1362C>T) in the general population?

CHRM1 p.Arg454= (c.1362C>T) is very rare (popmax 0.00266%, afr) (gnomAD).

CHRM1 p.Arg454=

c.1362C>T · VCV4912089

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

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 5.8	GERP -0.34, phastCons 1
Overall
CADD	11.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00266% African / African-American · 2/75,078 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,962 alleles · very rare exomes 1/1,461,586 · genomes 1/152,376 · joint denominator

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: CHRM1
Protein: p.Arg454=
Coding: c.1362C>T
MANE Select: NM_000738
Type: single nucleotide variant
Location: chr11:62909739 (GRCh38)
Gene constraint: LOEUF 0.325 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.51 · 7 PDB

Full CHRM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHRM1 p.Phe425Ser Likely pathogenic ★ same type
CHRM1 p.Ala26Asp Uncertain significance ★ ⚠ same type
CHRM1 p.Ala271Thr Uncertain significance ★ ⚠ same type
CHRM1 p.Arg137Cys Uncertain significance ★ ⚠ same type
CHRM1 p.Arg141Gln Uncertain significance ★ ⚠ same type
CHRM1 p.Arg213Gln Uncertain significance ★ ⚠ same type
CHRM1 p.Arg334His Uncertain significance ★ ⚠ same type
CHRM1 p.Arg336Gln 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/chrm1-p-arg454 (accessed [today's date]).

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