Is COL9A2 p.Pro437Arg (c.1310C>G) pathogenic?

COL9A2 p.Pro437Arg (c.1310C>G) is classified Uncertain significance in COL9A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-22). AlphaMissense: likely benign (0.1008); Very rare (popmax 0.000689%, nfe).

How common is COL9A2 p.Pro437Arg (c.1310C>G) in the general population?

COL9A2 p.Pro437Arg (c.1310C>G) is very rare (popmax 0.000689%, nfe) (gnomAD).

What do computational predictors say about COL9A2 p.Pro437Arg (c.1310C>G)?

AlphaMissense predicts likely benign (score 0.1008) — an in-silico prediction, not a clinical call.

COL9A2 p.Pro437Arg

c.1310C>G · rs777717075 · VCV1305905

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000689%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1008	likely benign
REVEL	0.667	pathogenic-leaning
SaProt	LLR -6.71	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.018 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000689% European (non-Finnish) · 8/1,161,310 alleles

Filtering AF 0.000296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000214%

Overall 0.000508% 8/1,574,570 alleles · very rare exomes 6/1,422,408 · genomes 2/152,162 · joint denominator

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.Pro437Arg
Coding: c.1310C>G
MANE Select: NM_001852
dbSNP: rs777717075
Type: single nucleotide variant
Location: chr1:40304077 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 437: the 'disordered' region; a UniProt-annotated variant site (sequence variant); 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.Pro437= Likely benign ★ 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-pro437arg (accessed [today's date]).

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