Is COL11A2 p.Pro1037= (c.3111G>T) pathogenic?

COL11A2 p.Pro1037= (c.3111G>T) is classified Benign/Likely benign in COL11A2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.28%, sas); Associated with fibrochondrogenesis 2.

What condition is associated with COL11A2 p.Pro1037= (c.3111G>T)?

COL11A2 p.Pro1037= (c.3111G>T) is associated with fibrochondrogenesis 2, connective tissue disorder, otospondylomegaepiphyseal dysplasia, autosomal recessive (ClinVar).

How common is COL11A2 p.Pro1037= (c.3111G>T) in the general population?

COL11A2 p.Pro1037= (c.3111G>T) is low-frequency (popmax 3.28%, sas) (gnomAD).

How is Fibrochondrogenesis inherited?

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

COL11A2 p.Pro1037=

c.3111G>T · rs146093235 · VCV197474

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.28%, sas)

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 -15	GERP -3.7
Overall
CADD	0.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.28% South Asian · 2,986/91,068 alleles

Filtering AF 3.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.14%

Overall 0.222% 3,587/1,612,914 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	3.28%	30
Remaining individualsnot grpmax-eligible	0.429%	233
East Asian	0.227%	440
Middle Eastern	0.132%	758
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
African / African-American	0.0786%	1,272
European (non-Finnish)	0.0105%	9,516
Admixed American	0.00666%	15,006

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.Pro1037=
Coding: c.3111G>T
MANE Select: NM_080680
dbSNP: rs146093235
Type: single nucleotide variant
Location: chr6:33171752 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1037: the 'disordered' region; the 'triple-helical region' region

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: connective tissue disorder otospondylomegaepiphyseal dysplasia, autosomal recessive

For Fibrochondrogenesis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal

Similar variants

COL11A2 p.Pro1037Leu 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
COL11A2 p.Gly1027Glu Likely pathogenic ★★ same condition
COL11A2 c.2682+5G>A Uncertain significance ★★ 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-pro1037 (accessed [today's date]).

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