Is COL11A2 p.Asp594= (c.1782C>T) pathogenic?

COL11A2 p.Asp594= (c.1782C>T) is classified Benign/Likely benign in COL11A2 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-06-01). Rare (popmax 0.79%, nfe); Associated with connective tissue disorder.

What condition is associated with COL11A2 p.Asp594= (c.1782C>T)?

COL11A2 p.Asp594= (c.1782C>T) is associated with connective tissue disorder, fibrochondrogenesis 2, otospondylomegaepiphyseal dysplasia, autosomal recessive (ClinVar).

How common is COL11A2 p.Asp594= (c.1782C>T) in the general population?

COL11A2 p.Asp594= (c.1782C>T) is rare (popmax 0.79%, nfe) (gnomAD).

COL11A2 p.Asp594=

c.1782C>T · rs41266697 · VCV46557

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

rare (popmax 0.79%, nfe)

Conditions

connective tissue disorder

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 -2.2	GERP -3.3
Overall
CADD	0.885	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.79% European (non-Finnish) · 9,326/1,179,814 alleles

Filtering AF 0.777% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.771%

Overall 0.756% 12,195/1,612,264 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.11%	47
European (non-Finnish)grpmax	0.79%	127
Remaining individualsnot grpmax-eligible	0.758%	132
South Asian	0.741%	135
African / African-American	0.617%	162
Middle Eastern	0.561%	178
Admixed American	0.487%	205
Finnishnot grpmax-eligible	0.471%	212
East Asian	0.029%	3,448

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.Asp594=
Coding: c.1782C>T
MANE Select: NM_080680
dbSNP: rs41266697
Type: single nucleotide variant
Location: chr6:33178344 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 594: the 'disordered' region; the 'triple-helical region' region

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fibrochondrogenesis 2 otospondylomegaepiphyseal dysplasia, autosomal recessive

Similar variants

COL11A2 p.Asp594Asn 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-asp594 (accessed [today's date]).

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