Is COL11A1 p.Pro1263= (c.3789A>G) pathogenic?

COL11A1 p.Pro1263= (c.3789A>G) is classified Benign/Likely benign in COL11A1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-07). Rare (popmax 0.473%, afr); Associated with fibrochondrogenesis 1.

What condition is associated with COL11A1 p.Pro1263= (c.3789A>G)?

COL11A1 p.Pro1263= (c.3789A>G) is associated with fibrochondrogenesis 1, Stickler syndrome type 2 (ClinVar).

How common is COL11A1 p.Pro1263= (c.3789A>G) in the general population?

COL11A1 p.Pro1263= (c.3789A>G) is rare (popmax 0.473%, afr) (gnomAD).

How is Fibrochondrogenesis inherited?

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

COL11A1 p.Pro1263=

c.3789A>G · rs144729226 · VCV291511

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.473%, afr)

Conditions

fibrochondrogenesis 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 -1.1	GERP -2.9, phastCons 0.002
Overall
CADD	3.923	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.473% African / African-American · 355/75,038 alleles

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

Overall 0.0249% 402/1,613,216 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.473%	211
Middle Eastern	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Admixed American	0.0333%	3,000
European (non-Finnish)	0.000254%	393,065

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.Pro1263=
Coding: c.3789A>G
MANE Select: NM_001854
dbSNP: rs144729226
Type: single nucleotide variant
Location: chr1:102915658 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 1263: the 'disordered' region; the 'triple-helical region' region

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

Disease context

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

Also linked: Stickler syndrome type 2

For Fibrochondrogenesis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal

Similar variants

COL11A1 p.Pro1263Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
COL11A1 p.Pro1263Ser 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-pro1263 (accessed [today's date]).

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