Is COL11A2 p.Ala193= (c.579C>T) pathogenic?

COL11A2 p.Ala193= (c.579C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-22). Very rare (popmax 0.00212%, nfe); Associated with fibrochondrogenesis 2.

How common is COL11A2 p.Ala193= (c.579C>T) in the general population?

COL11A2 p.Ala193= (c.579C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

How is Fibrochondrogenesis inherited?

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

COL11A2 p.Ala193=

Q: What condition is associated with COL11A2 p.Ala193= (c.579C>T)?

COL11A2 p.Ala193= (c.579C>T) is associated with fibrochondrogenesis 2, otospondylomegaepiphyseal dysplasia, autosomal dominant, otospondylomegaepiphyseal dysplasia, autosomal recessive (ClinVar).

c.579C>T · rs201054429 · VCV681633

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00212%, 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	GERP -2.2, phastCons 1
Overall
CADD	10.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,180,044 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00254% 41/1,612,914 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,974
European (non-Finnish)grpmax	0.00212%	47,202
Remaining individualsnot grpmax-eligible	0.0016%	62,476

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala193=
Coding: c.579C>T
MANE Select: NM_080680
dbSNP: rs201054429
Type: single nucleotide variant
Location: chr6:33188389 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 193: 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 dominant otospondylomegaepiphyseal dysplasia, autosomal recessive

For Fibrochondrogenesis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal

Similar variants

COL11A2 c.4392+1G>A Pathogenic ★★ same condition
COL11A2 p.Arg1020Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1331Ter Pathogenic ★★ same condition
COL11A2 p.Arg1379Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1600Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg379Ter 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-ala193 (accessed [today's date]).

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