Is COL11A2 p.Ala23fs (c.67dup) pathogenic?

COL11A2 p.Ala23fs (c.67dup) is classified Pathogenic in COL11A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-09). Absent from gnomAD; Associated with otospondylomegaepiphyseal dysplasia, autosomal recessive.

What condition is associated with COL11A2 p.Ala23fs (c.67dup)?

COL11A2 p.Ala23fs (c.67dup) is associated with otospondylomegaepiphyseal dysplasia, autosomal recessive (ClinVar).

How common is COL11A2 p.Ala23fs (c.67dup) in the general population?

COL11A2 p.Ala23fs (c.67dup) is absent from gnomAD (gnomAD).

COL11A2 p.Ala23fs

Q: How is Autosomal recessive otospondylomegaepiphyseal dysplasia inherited?

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

c.67dup · rs1583394539 · VCV802200

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

otospondylomegaepiphyseal dysplasia, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 66
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP 1.3, phastCons 0.71

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: COL11A2
Protein: p.Ala23fs
Coding: c.67dup
MANE Select: NM_080680
dbSNP: rs1583394539
Type: Duplication
Location: chr6:33192173 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18

Full COL11A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

otospondylomegaepiphyseal dysplasia, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive otospondylomegaepiphyseal dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

COL11A2 p.Gly1111fs Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Gly1279fs Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Ser864fs Likely pathogenic ★ same condition
COL11A2 p.Arg1020Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1331Ter Pathogenic ★★ same condition
COL11A2 p.Arg1600Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg433Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg558Ter 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/col11a2-p-ala23fs (accessed [today's date]).

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