Is COLQ p.Pro314= (c.942G>A) pathogenic?

COLQ p.Pro314= (c.942G>A) is classified Conflicting classifications of pathogenicity in COLQ (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-07-29). Ultra-rare (popmax 0.0173%, mid); Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Pro314= (c.942G>A)?

COLQ p.Pro314= (c.942G>A) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Pro314= (c.942G>A) in the general population?

COLQ p.Pro314= (c.942G>A) is ultra-rare (popmax 0.0173%, mid) (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.Pro314=

c.942G>A · rs771944316 · VCV343847

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, mid)

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 -9.4	GERP -4.1
Overall
CADD	2.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% Middle Eastern · 1/5,790 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00155% 25/1,613,648 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0173%	5,790
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Finnishnot grpmax-eligible	0.00469%	21,344
East Asian	0.00223%	44,886
Admixed American	0.00167%	59,996
European (non-Finnish)	0.00136%	73,751
African / African-American	0.00133%	74,908

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.Pro314=
Coding: c.942G>A
MANE Select: NM_005677
dbSNP: rs771944316
Type: single nucleotide variant
Location: chr3:15458198 (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 314: a UniProt-annotated variant site (in cms5; pathogenic)

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.Pro314Leu 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-pro314 (accessed [today's date]).

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