Is COLQ p.Pro143= (c.429T>C) pathogenic?

COLQ p.Pro143= (c.429T>C) is classified Likely benign in COLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-17). Very rare (popmax 0.00671%, eas); Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Pro143= (c.429T>C)?

COLQ p.Pro143= (c.429T>C) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Pro143= (c.429T>C) in the general population?

COLQ p.Pro143= (c.429T>C) is very rare (popmax 0.00671%, eas) (gnomAD).

How is Congenital myasthenic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COLQ p.Pro143=

c.429T>C · rs775589975 · VCV737301

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00671%, eas)

Conditions

congenital myasthenic syndrome 5

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 -0.73	GERP -1.7
Overall
CADD	6.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00671% East Asian · 3/44,728 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.000249% 4/1,607,104 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00671%	14,909
European (non-Finnish)	8.49e-05%	1,177,286

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.Pro143=
Coding: c.429T>C
MANE Select: NM_005677
dbSNP: rs775589975
Type: single nucleotide variant
Location: chr3:15477162 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 55.25 · 2 PDB
Residue 143: the collagen-like 1 domain; the 'disordered' region

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

Disease context

congenital myasthenic syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myasthenic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

COLQ p.Pro143His Uncertain significance ★ ⚠ 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
COLQ c.529-2A>G Pathogenic/Likely pathogenic ★★ same condition
COLQ c.555+1G>A Likely 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-pro143 (accessed [today's date]).

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