Is COL9A2 p.Ser673= (c.2019G>A) pathogenic?

COL9A2 p.Ser673= (c.2019G>A) is classified Conflicting classifications of pathogenicity in COL9A2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-05-12). Rare (popmax 0.554%, afr); Associated with epiphyseal dysplasia, multiple, 2.

What condition is associated with COL9A2 p.Ser673= (c.2019G>A)?

COL9A2 p.Ser673= (c.2019G>A) is associated with epiphyseal dysplasia, multiple, 2 (ClinVar).

How common is COL9A2 p.Ser673= (c.2019G>A) in the general population?

COL9A2 p.Ser673= (c.2019G>A) is rare (popmax 0.554%, afr) (gnomAD).

COL9A2 p.Ser673=

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.2019G>A · rs148008235 · VCV196777

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.554%, afr)

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 -1.8	GERP -1.5
Overall
CADD	7.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.554% African / African-American · 416/75,040 alleles

Filtering AF 0.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.493%

Overall 0.0312% 504/1,614,084 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.554%	180
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.0283%	3,531
European (non-Finnish)	0.00373%	26,819
East Asian	0.00223%	44,864
South Asian	0.0011%	91,076

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.Ser673=
Coding: c.2019G>A
MANE Select: NM_001852
dbSNP: rs148008235
Type: single nucleotide variant
Location: chr1:40301233 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 673: the 'nonhelical region 1 (nc1)' region; a UniProt-annotated variant site (sequence variant)

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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

COL9A2 p.Ser673Leu 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-ser673 (accessed [today's date]).

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