Is COL11A2 p.Arg151= (c.453T>C) pathogenic?

COL11A2 p.Arg151= (c.453T>C) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-05). Very rare (popmax 0.00186%, nfe); Associated with fibrochondrogenesis 2.

What condition is associated with COL11A2 p.Arg151= (c.453T>C)?

COL11A2 p.Arg151= (c.453T>C) is associated with fibrochondrogenesis 2, otospondylomegaepiphyseal dysplasia, autosomal recessive (ClinVar).

How common is COL11A2 p.Arg151= (c.453T>C) in the general population?

COL11A2 p.Arg151= (c.453T>C) is very rare (popmax 0.00186%, nfe) (gnomAD).

How is Fibrochondrogenesis inherited?

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

COL11A2 p.Arg151=

c.453T>C · rs147115504 · VCV356411

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 0.00186%, nfe)

Conditions

fibrochondrogenesis 2

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 -2.1	GERP -3.7
Overall
CADD	3.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,180,010 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,036 alleles · very rare exomes 22/1,460,734 · genomes 0/152,302 · joint denominator

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.Arg151=
Coding: c.453T>C
MANE Select: NM_080680
dbSNP: rs147115504
Type: single nucleotide variant
Location: chr6:33188515 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 151: the laminin g-like domain

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

Disease context

fibrochondrogenesis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: otospondylomegaepiphyseal dysplasia, autosomal recessive

For Fibrochondrogenesis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal

Similar variants

COL11A2 p.Arg151His Uncertain significance ★★ ⚠ same residue
COL11A2 p.Arg151Cys Uncertain significance ★ ⚠ same residue
COL11A2 p.Arg151Ser Uncertain significance ★ ⚠ same residue
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-arg151 (accessed [today's date]).

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