Is COLQ p.Arg402Pro (c.1205G>C) pathogenic?

COLQ p.Arg402Pro (c.1205G>C) is classified Uncertain significance in COLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely pathogenic (0.5676); Very rare (popmax 8.5e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COLQ p.Arg402Pro (c.1205G>C)?

COLQ p.Arg402Pro (c.1205G>C) is associated with Inborn genetic diseases (ClinVar).

How common is COLQ p.Arg402Pro (c.1205G>C) in the general population?

COLQ p.Arg402Pro (c.1205G>C) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about COLQ p.Arg402Pro (c.1205G>C)?

AlphaMissense predicts likely pathogenic (score 0.5676) — an in-silico prediction, not a clinical call.

COLQ p.Arg402Pro

c.1205G>C · VCV3495885

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5676	likely pathogenic
REVEL	0.712	pathogenic-leaning
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 70 kb · p 0.34 · regional, not allelic
Overall
CADD	24.8	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 8.5e-05% European (non-Finnish) · 1/1,176,464 alleles

Overall 6.87e-05% 1/1,454,868 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.Arg402Pro
Coding: c.1205G>C
MANE Select: NM_005677
Type: single nucleotide variant
Location: chr3:15453922 (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 402: 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

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

Similar variants

COLQ p.Arg402His Uncertain significance ★★ ⚠ same residue
COLQ p.Arg402Cys Uncertain significance ★ ⚠ same residue
COLQ p.Arg262Cys Uncertain significance ★★ ⚠ same condition
COLQ p.Arg290Lys Uncertain significance ★★ ⚠ same condition
COLQ p.Arg452His Uncertain significance ★★ ⚠ same condition
COLQ p.Arg45Cys Uncertain significance ★★ ⚠ same condition
COLQ p.Asp447Asn Uncertain significance ★★ ⚠ same condition
COLQ p.Cys52Arg Uncertain significance ★★ ⚠ 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-arg402pro (accessed [today's date]).

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