Is COLQ p.Asp416= (c.1248C>T) pathogenic?

COLQ p.Asp416= (c.1248C>T) is classified Benign in COLQ (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 5.09%, mid) — too common for a highly-penetrant pathogenic allele; Associated with congenital myasthenic syndrome 5.

What condition is associated with COLQ p.Asp416= (c.1248C>T)?

COLQ p.Asp416= (c.1248C>T) is associated with congenital myasthenic syndrome 5 (ClinVar).

How is Congenital myasthenic syndrome inherited?

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

COLQ p.Asp416=

Q: How common is COLQ p.Asp416= (c.1248C>T) in the general population?

COLQ p.Asp416= (c.1248C>T) is common (popmax 5.09%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1248C>T · rs55866379 · VCV128825

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 5.09%, mid) — too common for a highly-penetrant pathogenic allele

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 2.7	GERP 0.14, phastCons 1
Overall
CADD	8.954	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.09% Middle Eastern · 308/6,056 alleles

Filtering AF 4.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.44%

Overall 3.05% 49,248/1,612,056 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.09%	20
European (non-Finnish)	3.45%	29
Remaining individualsnot grpmax-eligible	3.19%	31
South Asian	3.1%	32
Admixed American	2.27%	44
Ashkenazi Jewishnot grpmax-eligible	1.67%	60
Finnishnot grpmax-eligible	1.62%	62
Amishnot grpmax-eligible	1.43%	70
African / African-American	0.811%	123
East Asian	0.00893%	11,196

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.Asp416=
Coding: c.1248C>T
MANE Select: NM_005677
dbSNP: rs55866379
Type: single nucleotide variant
Location: chr3:15453879 (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 416: 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-asp416 (accessed [today's date]).

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