Is COLQ p.Arg45Cys (c.133C>T) pathogenic?

COLQ p.Arg45Cys (c.133C>T) is classified Uncertain significance in COLQ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-18). AlphaMissense: likely benign (0.1897); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with COLQ p.Arg45Cys (c.133C>T)?

COLQ p.Arg45Cys (c.133C>T) is associated with Inborn genetic diseases, congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Arg45Cys (c.133C>T) in the general population?

COLQ p.Arg45Cys (c.133C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about COLQ p.Arg45Cys (c.133C>T)?

AlphaMissense predicts likely benign (score 0.1897) — an in-silico prediction, not a clinical call.

COLQ p.Arg45Cys

c.133C>T · rs763096476 · VCV195248

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1897 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1897	likely benign
REVEL	0.693	pathogenic-leaning
SaProt	LLR -7.76	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 70 kb · p 0.34 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.00833% Admixed American · 5/60,004 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00273% 44/1,614,014 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,001
South Asian	0.00769%	13,011
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00229%	43,704
East Asian	0.00223%	44,900

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: COLQ
Protein: p.Arg45Cys
Coding: c.133C>T
MANE Select: NM_005677
dbSNP: rs763096476
Type: single nucleotide variant
Location: chr3:15489611 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 55.25 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 5

Similar variants

COLQ p.Arg45His Uncertain significance ★ ⚠ same residue
COLQ p.Arg45Pro Uncertain significance ★ ⚠ same residue
COLQ p.Arg45= Likely benign ★ same residue
COLQ c.1195+1G>A Pathogenic ★★ same condition
COLQ c.1298+3A>G Pathogenic ★★ same condition
COLQ c.219+1G>C Pathogenic ★★ same condition
COLQ c.220-1G>A Pathogenic/Likely pathogenic ★★ same condition
COLQ c.393+1G>A Pathogenic ★★ same condition

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/colq-p-arg45cys (accessed [today's date]).

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