Is COLQ p.Ser100= (c.300C>T) pathogenic?

COLQ p.Ser100= (c.300C>T) is classified Benign/Likely benign in COLQ (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.15%, eas); Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Ser100= (c.300C>T)?

COLQ p.Ser100= (c.300C>T) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Ser100= (c.300C>T) in the general population?

COLQ p.Ser100= (c.300C>T) is low-frequency (popmax 1.15%, 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.Ser100=

c.300C>T · rs2305611 · VCV343854

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, 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 0.98	GERP -2.8, phastCons 1
Overall
CADD	7.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.15% East Asian · 514/44,884 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.038% 613/1,612,834 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.15%	87
South Asian	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Finnishnot grpmax-eligible	0.0112%	8,966
European (non-Finnish)	0.00322%	31,051
African / African-American	0.00266%	37,530
Admixed American	0.00167%	60,024

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.Ser100=
Coding: c.300C>T
MANE Select: NM_005677
dbSNP: rs2305611
Type: single nucleotide variant
Location: chr3:15488227 (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 100: 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 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
COLQ c.718-1276C>T 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-ser100 (accessed [today's date]).

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