Is COL11A2 p.Pro897fs (c.2690del) pathogenic?

COL11A2 p.Pro897fs (c.2690del) is classified Pathogenic/Likely pathogenic in COL11A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-12). Very rare (popmax 0.00167%, amr); Associated with otospondylomegaepiphyseal dysplasia, autosomal dominant.

What condition is associated with COL11A2 p.Pro897fs (c.2690del)?

COL11A2 p.Pro897fs (c.2690del) is associated with otospondylomegaepiphyseal dysplasia, autosomal dominant (ClinVar).

How common is COL11A2 p.Pro897fs (c.2690del) in the general population?

COL11A2 p.Pro897fs (c.2690del) is very rare (popmax 0.00167%, amr) (gnomAD).

COL11A2 p.Pro897fs

Q: How is Autosomal recessive otospondylomegaepiphyseal dysplasia inherited?

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

c.2690del · rs2150555528 · VCV1334054

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

otospondylomegaepiphyseal dysplasia, autosomal dominant

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 37 of 66
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.1	GERP -3.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Overall 6.85e-05% 1/1,460,746 alleles · very rare

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: COL11A2
Protein: p.Pro897fs
Coding: c.2690del
MANE Select: NM_080680
dbSNP: rs2150555528
Type: Deletion
Location: chr6:33173394 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 897: the 'disordered' region; the 'triple-helical region' region; the collagen-like 5 domain

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

Disease context

otospondylomegaepiphyseal dysplasia, autosomal dominant — 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 c.2734_2736+14del Likely pathogenic ★ same condition
COL11A2 p.Pro897= Uncertain significance ★ same residue
COL11A2 p.Pro897Leu Uncertain significance ★ ⚠ same residue
COL11A2 p.Pro897Ser Uncertain significance ★ ⚠ same residue
COL11A2 p.Glu941_Pro950delinsAla Pathogenic same condition
COL11A2 c.1719+3dup Likely pathogenic ★★ same condition
COL11A2 c.4392+1G>A Pathogenic ★★ same condition
COL11A2 p.Arg1020Ter 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/col11a2-p-pro897fs (accessed [today's date]).

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