Is COL9A2 p.Pro655= (c.1965A>G) pathogenic?

COL9A2 p.Pro655= (c.1965A>G) is classified Likely benign in COL9A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00446%, eas).

How common is COL9A2 p.Pro655= (c.1965A>G) in the general population?

COL9A2 p.Pro655= (c.1965A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

COL9A2 p.Pro655=

c.1965A>G · rs1225804636 · VCV2801408

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 -3.1	GERP -1.7
Overall
CADD	2.713	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,860 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000186% 3/1,613,322 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,430
Remaining individualsnot grpmax-eligible	0.0016%	62,402

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.Pro655=
Coding: c.1965A>G
MANE Select: NM_001852
dbSNP: rs1225804636
Type: single nucleotide variant
Location: chr1:40301287 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 655: the 'triple-helical region 1 (col1)' region; a UniProt-annotated variant site (sequence variant); the 'disordered' region

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

Similar variants

COL9A2 c.186+1G>A Pathogenic/Likely pathogenic ★★ same type
COL9A2 p.Arg136Ter Pathogenic/Likely pathogenic ★★ same type
COL9A2 p.Arg504Ter Pathogenic/Likely pathogenic ★★ same type
COL9A2 c.1107+4A>G Uncertain significance ★★ same type
COL9A2 c.1792+5G>A Uncertain significance ★★ same type
COL9A2 c.1793-9T>A Uncertain significance ★★ same type
COL9A2 c.1870+5G>C Uncertain significance ★★ same type
COL9A2 c.363+1G>A Uncertain significance ★★ same type

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-pro655 (accessed [today's date]).

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