Is COL2A1 p.Pro710= (c.2130C>T) pathogenic?

COL2A1 p.Pro710= (c.2130C>T) is classified Benign/Likely benign in COL2A1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-05). Rare (popmax 0.473%, afr); Associated with Stickler syndrome type 1.

What condition is associated with COL2A1 p.Pro710= (c.2130C>T)?

COL2A1 p.Pro710= (c.2130C>T) is associated with Stickler syndrome type 1, type 2 collagenopathy (ClinVar).

How common is COL2A1 p.Pro710= (c.2130C>T) in the general population?

COL2A1 p.Pro710= (c.2130C>T) is rare (popmax 0.473%, afr) (gnomAD).

How is Stickler syndrome inherited?

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

COL2A1 p.Pro710=

c.2130C>T · rs35656892 · VCV515646

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.473%, afr)

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 -11	GERP -3.5
Overall
CADD	0.184	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.473% African / African-American · 355/75,000 alleles

Filtering AF 0.433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.417%

Overall 0.035% 565/1,613,356 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.473%	211
Remaining individualsnot grpmax-eligible	0.072%	1,389
Middle Eastern	0.0495%	2,020
Admixed American	0.035%	2,858
South Asian	0.022%	4,553
European (non-Finnish)	0.0101%	9,915
Finnishnot grpmax-eligible	0.00315%	31,719

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.Pro710=
Coding: c.2130C>T
MANE Select: NM_001844
dbSNP: rs35656892
Type: single nucleotide variant
Location: chr12:47982911 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 710: 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

Also linked: type 2 collagenopathy

For Stickler syndrome (Orphanet):

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

Similar variants

COL2A1 p.Pro710Leu 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
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-pro710 (accessed [today's date]).

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