Is COL11A1 p.Pro1344= (c.4032G>A) pathogenic?

COL11A1 p.Pro1344= (c.4032G>A) is classified Conflicting classifications of pathogenicity in COL11A1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-07-13). Rare (popmax 0.134%, nfe); Associated with Stickler syndrome type 2.

What condition is associated with COL11A1 p.Pro1344= (c.4032G>A)?

COL11A1 p.Pro1344= (c.4032G>A) is associated with Stickler syndrome type 2, connective tissue disorder, fibrochondrogenesis 1 (ClinVar).

How common is COL11A1 p.Pro1344= (c.4032G>A) in the general population?

COL11A1 p.Pro1344= (c.4032G>A) is rare (popmax 0.134%, nfe) (gnomAD).

How is Stickler syndrome inherited?

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

COL11A1 p.Pro1344=

c.4032G>A · rs147637674 · VCV166922

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.134%, nfe)

Conditions

Stickler syndrome type 2

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 -1.7	GERP -3.6
Overall
CADD	14.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% European (non-Finnish) · 1,575/1,179,256 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.126%

Overall 0.112% 1,799/1,613,020 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.134%	749
Remaining individualsnot grpmax-eligible	0.114%	880
South Asian	0.102%	979
Middle Eastern	0.0826%	1,210
Admixed American	0.0584%	1,714
East Asian	0.0179%	5,597
African / African-American	0.00934%	10,709
Finnishnot grpmax-eligible	0.00781%	12,797

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: COL11A1
Protein: p.Pro1344=
Coding: c.4032G>A
MANE Select: NM_001854
dbSNP: rs147637674
Type: single nucleotide variant
Location: chr1:102913637 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 1344: the 'disordered' region; the 'triple-helical region' region

Full COL11A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: connective tissue disorder fibrochondrogenesis 1

For Stickler syndrome (Orphanet):

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

Similar variants

COL11A1 p.Pro1344Gln Uncertain significance ★★ ⚠ same residue
COL11A1 p.Pro1344Leu Uncertain significance ★★ ⚠ same residue
COL11A1 c.1245+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL11A1 c.1245+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL11A1 c.2241+5G>T Pathogenic/Likely pathogenic ★★ same condition
COL11A1 c.2808+1G>A Pathogenic ★★ same condition
COL11A1 c.2916+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL11A1 c.3762+2T>C 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/col11a1-p-pro1344 (accessed [today's date]).

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