Is COLQ p.Asp395= (c.1185C>T) pathogenic?

COLQ p.Asp395= (c.1185C>T) is classified Likely benign in COLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Very rare (popmax 0.00203%, nfe); Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Asp395= (c.1185C>T)?

COLQ p.Asp395= (c.1185C>T) is associated with congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Asp395= (c.1185C>T) in the general population?

COLQ p.Asp395= (c.1185C>T) is very rare (popmax 0.00203%, 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.Asp395=

c.1185C>T · rs548322139 · VCV1128865

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

Conditions

congenital myasthenic syndrome 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.63 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.1	GERP -4.3
Overall
CADD	10.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,968 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00173% 28/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,165
Admixed American	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,016
South Asian	0.0011%	91,090

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.Asp395=
Coding: c.1185C>T
MANE Select: NM_005677
dbSNP: rs548322139
Type: single nucleotide variant
Location: chr3:15455909 (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 395: 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); a UniProt-annotated variant site (in cms5; likely 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 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-asp395 (accessed [today's date]).

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