Is COLQ p.Pro263= (c.789G>A) pathogenic?

COLQ p.Pro263= (c.789G>A) is classified Benign/Likely benign in COLQ (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Rare (popmax 0.818%, afr); Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Pro263= (c.789G>A)?

COLQ p.Pro263= (c.789G>A) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Pro263= (c.789G>A) in the general population?

COLQ p.Pro263= (c.789G>A) is rare (popmax 0.818%, afr) (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.Pro263=

c.789G>A · rs150061580 · VCV468348

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.818%, afr)

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 -3.8	GERP -4.9
Overall
CADD	4.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.818% African / African-American · 614/75,052 alleles

Filtering AF 0.765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.743%

Overall 0.0475% 766/1,614,054 alleles · rare exomes 411/1,461,730 · genomes 355/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.818%	122
Admixed American	0.0999%	1,001
Remaining individualsnot grpmax-eligible	0.0896%	1,116
Middle Eastern	0.066%	1,516
East Asian	0.00446%	22,440
European (non-Finnish)	0.00246%	40,689
South Asian	0.0011%	91,080

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.Pro263=
Coding: c.789G>A
MANE Select: NM_005677
dbSNP: rs150061580
Type: single nucleotide variant
Location: chr3:15466366 (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 263: the collagen-like 1 domain; a UniProt-annotated variant site (in cms5; pathogenic); 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.Pro263Leu 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-pro263 (accessed [today's date]).

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