Is COL2A1 p.Pro484= (c.1452C>T) pathogenic?

COL2A1 p.Pro484= (c.1452C>T) is classified Likely benign in COL2A1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-14). Very rare (popmax 0.00239%, eas); Associated with Stickler syndrome type 1.

What condition is associated with COL2A1 p.Pro484= (c.1452C>T)?

COL2A1 p.Pro484= (c.1452C>T) is associated with Stickler syndrome type 1 (ClinVar).

How common is COL2A1 p.Pro484= (c.1452C>T) in the general population?

COL2A1 p.Pro484= (c.1452C>T) is very rare (popmax 0.00239%, eas) (gnomAD).

How is Stickler syndrome inherited?

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

COL2A1 p.Pro484=

c.1452C>T · rs755093756 · VCV403714

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00239%, eas)

Conditions

Stickler syndrome type 1

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 -0.76	GERP -3.8
Overall
CADD	7.228	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00239% East Asian · 1/41,912 alleles

Filtering AF 0.000975% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000805%

Overall 0.00134% 21/1,562,750 alleles · very rare exomes 20/1,410,760 · genomes 1/151,990 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00239%	41,912
Remaining individualsnot grpmax-eligible	0.00165%	60,508
European (non-Finnish)	0.00156%	64,070
South Asian	0.00118%	84,934

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: COL2A1
Protein: p.Pro484=
Coding: c.1452C>T
MANE Select: NM_001844
dbSNP: rs755093756
Type: single nucleotide variant
Location: chr12:47986411 (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

Stickler syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Stickler syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

COL2A1 p.Pro484Thr Uncertain significance ★ ⚠ same residue
COL2A1 p.Pro484Ser Likely benign ★ same residue
COL2A1 c.1222-2A>G Pathogenic ★★ same condition
COL2A1 c.1365+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL2A1 c.1420-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL2A1 c.1527+135G>A Pathogenic/Likely pathogenic ★★ same condition
COL2A1 c.1833+1G>A Pathogenic ★★ same condition
COL2A1 c.1887+1G>A Pathogenic/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-pro484 (accessed [today's date]).

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