Is COLQ p.Pro361Ser (c.1081C>T) pathogenic?

COLQ p.Pro361Ser (c.1081C>T) is classified Benign/Likely benign in COLQ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1035); Rare (popmax 0.905%, eas); Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Pro361Ser (c.1081C>T)?

COLQ p.Pro361Ser (c.1081C>T) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Pro361Ser (c.1081C>T) in the general population?

COLQ p.Pro361Ser (c.1081C>T) is rare (popmax 0.905%, eas) (gnomAD).

How is Congenital myasthenic syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about COLQ p.Pro361Ser (c.1081C>T)?

AlphaMissense predicts likely benign (score 0.1035) — an in-silico prediction, not a clinical call.

COLQ p.Pro361Ser

c.1081C>T · rs116828761 · VCV343846

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1035 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.905%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 5

Computational evidence

Protein change
AlphaMissense	0.1035	likely benign
REVEL	0.707	pathogenic-leaning
SaProt	LLR -6.31	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 70 kb · p 0.34 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.905% East Asian · 406/44,866 alleles

Filtering AF 0.832% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.804%

Overall 0.0387% 624/1,613,998 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.905%	111
South Asian	0.144%	695
Remaining individualsnot grpmax-eligible	0.107%	933
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,920
Middle Eastern	0.0165%	6,062
African / African-American	0.008%	12,502
Admixed American	0.00333%	29,995
European (non-Finnish)	0.000508%	196,663

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.Pro361Ser
Coding: c.1081C>T
MANE Select: NM_005677
dbSNP: rs116828761
Type: single nucleotide variant
Location: chr3:15456013 (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 361: a UniProt-annotated variant site (in cms5; pathogenic); a UniProt-annotated variant site (in cms5; pathogenic; impaired anchoring of asymmetric ache to the synaptic basal membrane)

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.Pro361fs Pathogenic ★★ 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-pro361ser (accessed [today's date]).

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