Is COL11A1 p.Ala596fs (c.1786dup) pathogenic?

COL11A1 p.Ala596fs (c.1786dup) is classified Pathogenic in COL11A1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2010-11-12). Absent from gnomAD; Associated with fibrochondrogenesis.

What condition is associated with COL11A1 p.Ala596fs (c.1786dup)?

COL11A1 p.Ala596fs (c.1786dup) is associated with fibrochondrogenesis (ClinVar).

How common is COL11A1 p.Ala596fs (c.1786dup) in the general population?

COL11A1 p.Ala596fs (c.1786dup) is absent from gnomAD (gnomAD).

How is Fibrochondrogenesis inherited?

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

COL11A1 p.Ala596fs

c.1786dup · rs730882190 · VCV29646

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

fibrochondrogenesis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 17 of 67
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL11A1
Protein: p.Ala596fs
Coding: c.1786dup
MANE Select: NM_001854
dbSNP: rs730882190
Type: Duplication
Location: chr1:103006072 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 596: the 'disordered' region; the 'triple-helical region' region; the collagen-like 3 domain

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

Disease context

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

For Fibrochondrogenesis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal

Similar variants

COL11A1 p.Ala596Ser Uncertain significance ★ ⚠ same residue
COL11A1 p.Ala596Thr Likely benign ★ ⚠ same residue
COL11A1 p.Glu1088Ala Uncertain significance ★★ ⚠ same condition
COL11A1 p.Gly1315Ter Pathogenic ★ same condition
COL11A1 p.Gly1081Arg Uncertain significance ★ ⚠ same condition
COL11A1 p.Gly1414Cys Uncertain significance ★ ⚠ same condition
COL11A1 p.Val303Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
COL11A1 p.Gly784Arg 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-ala596fs (accessed [today's date]).

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