Is COLQ p.Pro265His (c.794C>A) pathogenic?

COLQ p.Pro265His (c.794C>A) is classified Uncertain significance in COLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely benign (0.1254); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COLQ p.Pro265His (c.794C>A)?

COLQ p.Pro265His (c.794C>A) is associated with Inborn genetic diseases (ClinVar).

How common is COLQ p.Pro265His (c.794C>A) in the general population?

COLQ p.Pro265His (c.794C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COLQ p.Pro265His (c.794C>A)?

AlphaMissense predicts likely benign (score 0.1254) — an in-silico prediction, not a clinical call.

COLQ p.Pro265His

c.794C>A · VCV4005671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1254 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1254	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 70 kb · p 0.34 · regional, not allelic
Overall
CADD	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COLQ
Protein: p.Pro265His
Coding: c.794C>A
MANE Select: NM_005677
Type: single nucleotide variant
Location: chr3:15466361 (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 265: the collagen-like 1 domain; a UniProt-annotated variant site (in cms5; pathogenic); 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

Similar variants

COLQ p.Pro265Leu Uncertain significance ★ ⚠ same residue
COLQ p.Pro265fs Pathogenic ★★ same residue
COLQ p.Arg262Cys Uncertain significance ★★ ⚠ same condition
COLQ p.Arg290Lys Uncertain significance ★★ ⚠ same condition
COLQ p.Arg402His 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

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-pro265his (accessed [today's date]).

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