Is COL9A2 p.Glu608= (c.1824A>G) pathogenic?

COL9A2 p.Glu608= (c.1824A>G) is classified Likely benign in COL9A2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0488%, nfe); Associated with epiphyseal dysplasia, multiple, 2.

What condition is associated with COL9A2 p.Glu608= (c.1824A>G)?

COL9A2 p.Glu608= (c.1824A>G) is associated with epiphyseal dysplasia, multiple, 2, connective tissue disorder (ClinVar).

How common is COL9A2 p.Glu608= (c.1824A>G) in the general population?

COL9A2 p.Glu608= (c.1824A>G) is ultra-rare (popmax 0.0488%, nfe) (gnomAD).

COL9A2 p.Glu608=

Q: How is Multiple epiphyseal dysplasia due to collagen 9 anomaly inherited?

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

c.1824A>G · rs138949427 · VCV297292

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0488%, nfe)

Conditions

epiphyseal dysplasia, multiple, 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 -0.8	GERP -3.9
Overall
CADD	5.972	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0488% European (non-Finnish) · 576/1,180,012 alleles

Filtering AF 0.0455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0442%

Overall 0.0369% 595/1,614,024 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0488%	2,049
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Admixed American	0.00667%	15,002
Finnishnot grpmax-eligible	0.00469%	21,345
African / African-American	0.004%	24,981

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: COL9A2
Protein: p.Glu608=
Coding: c.1824A>G
MANE Select: NM_001852
dbSNP: rs138949427
Type: single nucleotide variant
Location: chr1:40301858 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 608: a UniProt-annotated variant site (sequence variant); the 'triple-helical region 2 (col2)' region; the 'disordered' region

Full COL9A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: connective tissue disorder

For Multiple epiphyseal dysplasia due to collagen 9 anomaly (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

COL9A2 p.Glu608Asp Uncertain significance ★ ⚠ same residue
COL9A2 c.186+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL9A2 c.*67A>G Uncertain significance ★★ same condition
COL9A2 p.Arg136Gln Uncertain significance ★★ ⚠ same condition
COL9A2 p.Arg375Leu Uncertain significance ★★ ⚠ same condition
COL9A2 p.Asp428His Uncertain significance ★★ ⚠ same condition
COL9A2 p.Asp519His Uncertain significance ★★ ⚠ same condition
COL9A2 p.Gly250Ala 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/col9a2-p-glu608 (accessed [today's date]).

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