Is COL9A2 p.Pro62= (c.186G>C) pathogenic?

COL9A2 p.Pro62= (c.186G>C) is classified Pathogenic in COL9A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-12-24). Absent from gnomAD v4.1; Associated with epiphyseal dysplasia, multiple, 2.

What condition is associated with COL9A2 p.Pro62= (c.186G>C)?

COL9A2 p.Pro62= (c.186G>C) is associated with epiphyseal dysplasia, multiple, 2 (ClinVar).

How common is COL9A2 p.Pro62= (c.186G>C) in the general population?

COL9A2 p.Pro62= (c.186G>C) is absent from gnomAD v4.1 (gnomAD).

COL9A2 p.Pro62=

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.186G>C · rs1085307973 · VCV17146

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

epiphyseal dysplasia, multiple, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.074	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.27	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.8	GERP 0.82, phastCons 1
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL9A2
Protein: p.Pro62=
Coding: c.186G>C
MANE Select: NM_001852
dbSNP: rs1085307973
Type: single nucleotide variant
Location: chr1:40314352 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 62: 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 p.Pro62Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro62 (accessed [today's date]).

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