Is COL11A1 p.Ile337= (c.1011A>T) pathogenic?

COL11A1 p.Ile337= (c.1011A>T) is classified Conflicting classifications of pathogenicity in COL11A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-18). Ultra-rare (popmax 0.034%, sas); Associated with fibrochondrogenesis 1.

What condition is associated with COL11A1 p.Ile337= (c.1011A>T)?

COL11A1 p.Ile337= (c.1011A>T) is associated with fibrochondrogenesis 1, Stickler syndrome type 2 (ClinVar).

How common is COL11A1 p.Ile337= (c.1011A>T) in the general population?

COL11A1 p.Ile337= (c.1011A>T) is ultra-rare (popmax 0.034%, sas) (gnomAD).

How is Fibrochondrogenesis inherited?

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

COL11A1 p.Ile337=

c.1011A>T · rs563115409 · VCV291538

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

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 0.2	GERP -2.5, phastCons 0.96
Overall
CADD	6.443	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% South Asian · 31/91,066 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00205% 33/1,613,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.034%	2,938
Remaining individualsnot grpmax-eligible	0.0032%	31,240

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.Ile337=
Coding: c.1011A>T
MANE Select: NM_001854
dbSNP: rs563115409
Type: single nucleotide variant
Location: chr1:103022976 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 337: the 'nonhelical 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.Ile337Val Likely benign ★ 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
COL11A1 c.3816+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/col11a1-p-ile337 (accessed [today's date]).

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