Is COL9A2 p.Pro614= (c.1842C>T) pathogenic?

COL9A2 p.Pro614= (c.1842C>T) is classified Likely benign in COL9A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-16). Very rare (popmax 0.00668%, eas).

How common is COL9A2 p.Pro614= (c.1842C>T) in the general population?

COL9A2 p.Pro614= (c.1842C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

COL9A2 p.Pro614=

c.1842C>T · rs763724733 · VCV1625848

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, 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 -8.9	GERP -4.1
Overall
CADD	0.953	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,900 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00291% 47/1,613,956 alleles · very rare exomes 46/1,461,718 · genomes 1/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,967
Admixed American	0.00667%	15,001
Remaining individualsnot grpmax-eligible	0.0048%	20,821
European (non-Finnish)	0.00297%	33,714
African / African-American	0.00267%	37,472

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.Pro614=
Coding: c.1842C>T
MANE Select: NM_001852
dbSNP: rs763724733
Type: single nucleotide variant
Location: chr1:40301840 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.99 · 4 PDB
Residue 614: a UniProt-annotated variant site (sequence variant); the 'triple-helical region 2 (col2)' region; the 'disordered' region

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

Similar variants

COL9A2 p.Pro614Arg 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-pro614 (accessed [today's date]).

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