Is COL9A2 p.Pro35fs (c.104del) pathogenic?

COL9A2 p.Pro35fs (c.104del) is classified Pathogenic in COL9A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-04). Very rare (popmax 0.00196%, amr).

How common is COL9A2 p.Pro35fs (c.104del) in the general population?

COL9A2 p.Pro35fs (c.104del) is very rare (popmax 0.00196%, amr) (gnomAD).

COL9A2 p.Pro35fs

c.104del · rs761125486 · VCV1959013

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00196%, amr)

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 2 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.89	GERP -3.7, phastCons 0.003

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00196% Admixed American · 1/51,066 alleles

Overall 0.000143% 2/1,401,582 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00196%	51,066
European (non-Finnish)	8.71e-05%	1,147,818

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.Pro35fs
Coding: c.104del
MANE Select: NM_001852
dbSNP: rs761125486
Type: Deletion
Location: chr1:40315636 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 35: the 'disordered' region; the 'triple-helical region 4 (col4)' region

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

Similar variants

COL9A2 p.Pro35= Likely benign ★ 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-pro35fs (accessed [today's date]).

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