Is COL9A2 p.Pro104= (c.312C>T) pathogenic?

COL9A2 p.Pro104= (c.312C>T) is classified Benign/Likely benign in COL9A2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-28). Rare (popmax 0.684%, afr); Associated with epiphyseal dysplasia, multiple, 2.

What condition is associated with COL9A2 p.Pro104= (c.312C>T)?

COL9A2 p.Pro104= (c.312C>T) is associated with epiphyseal dysplasia, multiple, 2 (ClinVar).

How common is COL9A2 p.Pro104= (c.312C>T) in the general population?

COL9A2 p.Pro104= (c.312C>T) is rare (popmax 0.684%, afr) (gnomAD).

COL9A2 p.Pro104=

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.312C>T · rs144072834 · VCV198137

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.684%, afr)

Conditions

epiphyseal dysplasia, multiple, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.311	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -3.1
Overall
CADD	1.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.684% African / African-American · 513/75,044 alleles

Filtering AF 0.635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.615%

Overall 0.0359% 580/1,614,052 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.684%	146
Remaining individualsnot grpmax-eligible	0.0448%	2,232
Admixed American	0.0317%	3,158
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,354
European (non-Finnish)	0.00136%	73,749

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.Pro104=
Coding: c.312C>T
MANE Select: NM_001852
dbSNP: rs144072834
Type: single nucleotide variant
Location: chr1:40312601 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 104: the 'disordered' region; the 'triple-helical region 4 (col4)' 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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

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
COL9A2 p.Gly274Ser 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-pro104 (accessed [today's date]).

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