Is COL9A2 p.Pro80= (c.240C>T) pathogenic?

COL9A2 p.Pro80= (c.240C>T) is classified Likely benign in COL9A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-12). Very rare (popmax 0.00229%, nfe).

How common is COL9A2 p.Pro80= (c.240C>T) in the general population?

COL9A2 p.Pro80= (c.240C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

COL9A2 p.Pro80=

c.240C>T · rs372016237 · VCV1328582

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.088	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.5
Overall
CADD	0.195	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,180,018 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00173% 28/1,614,028 alleles · very rare exomes 26/1,461,882 · genomes 2/152,146 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,704
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Pro80=
Coding: c.240C>T
MANE Select: NM_001852
dbSNP: rs372016237
Type: single nucleotide variant
Location: chr1:40314214 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 80: 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.Pro80His Uncertain significance ★ ⚠ same residue
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

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-pro80 (accessed [today's date]).

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