Is COL2A1 p.Pro484fs (c.1449dup) pathogenic?

COL2A1 p.Pro484fs (c.1449dup) is classified Pathogenic in COL2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). Associated with Inborn genetic diseases.

What condition is associated with COL2A1 p.Pro484fs (c.1449dup)?

COL2A1 p.Pro484fs (c.1449dup) is associated with Inborn genetic diseases (ClinVar).

COL2A1 p.Pro484fs

c.1449dup · VCV4616232

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 23 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: COL2A1
Protein: p.Pro484fs
Coding: c.1449dup
MANE Select: NM_001844
Type: Duplication
Location: chr12:47986413 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 484: the 'disordered' region; the 'triple-helical region' region

Full COL2A1 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

COL2A1 p.Gly1215fs Pathogenic ★ same condition
COL2A1 p.Pro484Thr Uncertain significance ★ ⚠ same residue
COL2A1 p.Pro484= Likely benign ★ same residue
COL2A1 p.Pro484Ser Likely benign ★ same residue
COL2A1 p.Cys52Ter Pathogenic/Likely pathogenic ★★ same condition
COL2A1 p.Gln39Ter Pathogenic ★★ same condition
COL2A1 p.Gly546Ser Pathogenic/Likely pathogenic ★★ same condition
COL2A1 p.Gly930Asp 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/col2a1-p-pro484fs (accessed [today's date]).

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