Is COL11A1 p.Ala447= (c.1341A>G) pathogenic?

COL11A1 p.Ala447= (c.1341A>G) is classified Conflicting classifications of pathogenicity in COL11A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-19). Very rare (popmax 0.00467%, nfe); Associated with fibrochondrogenesis 1.

What condition is associated with COL11A1 p.Ala447= (c.1341A>G)?

COL11A1 p.Ala447= (c.1341A>G) is associated with fibrochondrogenesis 1, Stickler syndrome type 2 (ClinVar).

How common is COL11A1 p.Ala447= (c.1341A>G) in the general population?

COL11A1 p.Ala447= (c.1341A>G) is very rare (popmax 0.00467%, nfe) (gnomAD).

How is Fibrochondrogenesis inherited?

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

COL11A1 p.Ala447=

c.1341A>G · rs372963982 · VCV875886

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00467%, nfe)

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 -0.33	GERP -1.4, phastCons 0.35
Overall
CADD	9.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00467% European (non-Finnish) · 55/1,178,714 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00366% 59/1,612,276 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00467%	21,431
Remaining individualsnot grpmax-eligible	0.00321%	31,198
African / African-American	0.00267%	37,440

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.Ala447=
Coding: c.1341A>G
MANE Select: NM_001854
dbSNP: rs372963982
Type: single nucleotide variant
Location: chr1:103018827 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 447: the 'triple-helical region (interrupted)' region; the 'disordered' region; the collagen-like 1 domain

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 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
COL11A1 c.3816+1G>A Pathogenic ★★ same condition
COL11A1 c.4554+1G>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-ala447 (accessed [today's date]).

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