Is COLQ p.Ser257fs (c.769dup) pathogenic?

COLQ p.Ser257fs (c.769dup) is classified Pathogenic in COLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-31). Absent from gnomAD; Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Ser257fs (c.769dup)?

COLQ p.Ser257fs (c.769dup) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Ser257fs (c.769dup) in the general population?

COLQ p.Ser257fs (c.769dup) is absent from gnomAD (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.Ser257fs

c.769dup · rs2062200939 · VCV965255

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12	GERP 2.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COLQ
Protein: p.Ser257fs
Coding: c.769dup
MANE Select: NM_005677
dbSNP: rs2062200939
Type: Duplication
Location: chr3:15466385 (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 257: 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.Ser257Ala 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.Pro265fs Pathogenic ★★ same condition
COLQ p.Gln107fs Likely pathogenic ★ same condition
COLQ p.Leu37fs Pathogenic ★ same condition
COLQ p.Phe284fs 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-ser257fs (accessed [today's date]).

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