Is COL9A2 p.Pro186fs (c.557del) pathogenic?

COL9A2 p.Pro186fs (c.557del) is classified Pathogenic in COL9A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). Very rare (popmax 0.000254%, nfe).

How common is COL9A2 p.Pro186fs (c.557del) in the general population?

COL9A2 p.Pro186fs (c.557del) is very rare (popmax 0.000254%, nfe) (gnomAD).

COL9A2 p.Pro186fs

c.557del · rs749888464 · VCV1375958

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.2	GERP -3.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,004 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,860 alleles · very rare

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.Pro186fs
Coding: c.557del
MANE Select: NM_001852
dbSNP: rs749888464
Type: Deletion
Location: chr1:40311249 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 186: the 'disordered' region; the 'triple-helical region 3 (col3)' region

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

Similar variants

COL9A2 p.Pro186Leu Uncertain significance ★ ⚠ same residue
COL9A2 p.Asn503fs Pathogenic/Likely pathogenic ★★ same type
COL9A2 p.Gly412fs Pathogenic ★★ same type
COL9A2 p.Gly415fs Pathogenic/Likely pathogenic ★★ same type
COL9A2 p.Leu537fs Pathogenic/Likely pathogenic ★★ same type
COL9A2 p.Lys243fs Pathogenic ★★ same type
COL9A2 c.1008+3_1008+6del Uncertain significance ★★ same type
COL9A2 c.1603+18del Benign/Likely benign ★★ 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-pro186fs (accessed [today's date]).

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