Is COLQ p.Pro128Ala (c.382C>G) pathogenic?

COLQ p.Pro128Ala (c.382C>G) is classified Uncertain significance in COLQ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1601); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with COLQ p.Pro128Ala (c.382C>G)?

COLQ p.Pro128Ala (c.382C>G) is associated with Inborn genetic diseases, congenital myasthenic syndrome 5 (ClinVar).

How common is COLQ p.Pro128Ala (c.382C>G) in the general population?

COLQ p.Pro128Ala (c.382C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about COLQ p.Pro128Ala (c.382C>G)?

AlphaMissense predicts likely benign (score 0.1601) — an in-silico prediction, not a clinical call.

COLQ p.Pro128Ala

c.382C>G · rs1230299116 · VCV1986219

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1601 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1601	likely benign
REVEL	0.664	pathogenic-leaning
SaProt	LLR -6.57	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 12	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 70 kb · p 0.34 · regional, not allelic
Overall
CADD	25.0	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 0.005% Admixed American · 3/60,022 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,888 alleles · very rare

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.Pro128Ala
Coding: c.382C>G
MANE Select: NM_005677
dbSNP: rs1230299116
Type: single nucleotide variant
Location: chr3:15478988 (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 128: the collagen-like 1 domain; the 'disordered' region

Full COLQ gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 5

Similar variants

COLQ p.Pro128Leu 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-pro128ala (accessed [today's date]).

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