Is COL2A1 p.Pro169= (c.507C>T) pathogenic?

COL2A1 p.Pro169= (c.507C>T) is classified Benign/Likely benign in COL2A1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-05-11). Rare (popmax 0.169%, nfe); Associated with type 2 collagenopathy.

What condition is associated with COL2A1 p.Pro169= (c.507C>T)?

COL2A1 p.Pro169= (c.507C>T) is associated with type 2 collagenopathy, Stickler syndrome type 1 (ClinVar).

How common is COL2A1 p.Pro169= (c.507C>T) in the general population?

COL2A1 p.Pro169= (c.507C>T) is rare (popmax 0.169%, nfe) (gnomAD).

COL2A1 p.Pro169=

c.507C>T · rs143851987 · VCV308935

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.169%, nfe)

Conditions

type 2 collagenopathy

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 -0.54	GERP -3.2
Overall
CADD	6.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% European (non-Finnish) · 1,993/1,179,878 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.14% 2,257/1,613,802 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.329%	304
European (non-Finnish)grpmax	0.169%	592
South Asian	0.131%	765
Remaining individualsnot grpmax-eligible	0.0992%	1,008
Middle Eastern	0.0825%	1,212
Ashkenazi Jewishnot grpmax-eligible	0.0574%	1,742
Admixed American	0.0383%	2,610
Finnishnot grpmax-eligible	0.0282%	3,549
African / African-American	0.0227%	4,411

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro169=
Coding: c.507C>T
MANE Select: NM_001844
dbSNP: rs143851987
Type: single nucleotide variant
Location: chr12:47997630 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 169: the 'disordered' region

Full COL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

type 2 collagenopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Stickler syndrome type 1

Similar variants

COL2A1 p.Pro169His Conflicting classifications of pathogenicity ★ ⚠ same residue
COL2A1 p.Pro169Thr Conflicting classifications of pathogenicity ★ ⚠ 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.1581+1G>A Likely pathogenic ★★ same condition
COL2A1 c.1833+1G>A 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-pro169 (accessed [today's date]).

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