Is COL11A2 p.Asp900= (c.2700T>C) pathogenic?

COL11A2 p.Asp900= (c.2700T>C) is classified Benign in COL11A2 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-05-08). Common (popmax 98.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with fibrochondrogenesis 2.

How is Fibrochondrogenesis inherited?

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

COL11A2 p.Asp900=

Q: What condition is associated with COL11A2 p.Asp900= (c.2700T>C)?

COL11A2 p.Asp900= (c.2700T>C) is associated with fibrochondrogenesis 2, otospondylomegaepiphyseal dysplasia, autosomal dominant, autosomal dominant nonsyndromic hearing loss 13 (ClinVar).

Q: How common is COL11A2 p.Asp900= (c.2700T>C) in the general population?

COL11A2 p.Asp900= (c.2700T>C) is common (popmax 98.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2700T>C · rs2229785 · VCV46562

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 98.9%, eas) — too common for a highly-penetrant pathogenic allele

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 -9.1	GERP -3.7
Overall
CADD	0.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 98.9% East Asian · 44,342/44,824 alleles

Filtering AF 98.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 97.8%

Overall 75.1% 1,211,313/1,612,256 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	98.9%	1
South Asian	89.2%	1
African / African-American	88.2%	1
Ashkenazi Jewishnot grpmax-eligible	84.4%	1
Middle Eastern	83.4%	1
Admixed American	80.6%	1
Remaining individualsnot grpmax-eligible	77%	1
European (non-Finnish)	71.9%	1
Finnishnot grpmax-eligible	70.6%	1
Amishnot grpmax-eligible	62.8%	2

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.Asp900=
Coding: c.2700T>C
MANE Select: NM_080680
dbSNP: rs2229785
Type: single nucleotide variant
Location: chr6:33173384 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 900: 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: otospondylomegaepiphyseal dysplasia, autosomal dominant autosomal dominant nonsyndromic hearing loss 13 autosomal recessive nonsyndromic hearing loss 53 otospondylomegaepiphyseal dysplasia, autosomal recessive

For Fibrochondrogenesis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal

Similar variants

COL11A2 p.Asp900Glu Uncertain significance ★ ⚠ same residue
COL11A2 p.Asp900His Uncertain significance ★ ⚠ same residue
COL11A2 c.1819-2A>G Likely pathogenic ★★ same condition
COL11A2 c.3852+1G>T Likely pathogenic ★★ same condition
COL11A2 c.4392+1G>A Pathogenic ★★ same condition
COL11A2 p.Arg1020Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1034Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL11A2 p.Arg1331Ter 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-asp900 (accessed [today's date]).

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