Is COLQ p.Pro265fs (c.788dup) pathogenic?

COLQ p.Pro265fs (c.788dup) is classified Pathogenic in COLQ (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-11). Very rare (popmax 0.00466%, nfe); Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Pro265fs (c.788dup)?

COLQ p.Pro265fs (c.788dup) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Pro265fs (c.788dup) in the general population?

COLQ p.Pro265fs (c.788dup) is very rare (popmax 0.00466%, nfe) (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.Pro265fs

c.788dup · rs759911990 · VCV6653

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00466%, nfe)

Conditions

congenital myasthenic syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.8	GERP -4.9
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00466% European (non-Finnish) · 55/1,179,992 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00341% 55/1,613,938 alleles · very rare

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.Pro265fs
Coding: c.788dup
MANE Select: NM_005677
dbSNP: rs759911990
Type: Duplication
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 265: 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.Pro265Leu Uncertain significance ★ ⚠ same residue
COLQ p.Asn81fs Pathogenic ★★ same condition
COLQ p.His409fs Pathogenic/Likely pathogenic ★★ same condition
COLQ p.Leu53fs Pathogenic ★★ same condition
COLQ p.Gln107fs Likely pathogenic ★ same condition
COLQ p.Leu37fs Pathogenic ★ same condition
COLQ p.Phe284fs Likely pathogenic ★ same condition
COLQ p.Ser257fs 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-pro265fs (accessed [today's date]).

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