Is COL2A1 p.Arg904= (c.2712C>T) pathogenic?

COL2A1 p.Arg904= (c.2712C>T) is classified Likely benign in COL2A1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-10). Ultra-rare (popmax 0.0187%, afr).

How common is COL2A1 p.Arg904= (c.2712C>T) in the general population?

COL2A1 p.Arg904= (c.2712C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

COL2A1 p.Arg904=

c.2712C>T · rs765332234 · VCV515600

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

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 -9.8	GERP -3.5
Overall
CADD	7.263	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,836 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00136% 22/1,613,420 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,345
East Asian	0.00446%	22,443
European (non-Finnish)	0.000508%	196,658

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: COL2A1
Protein: p.Arg904=
Coding: c.2712C>T
MANE Select: NM_001844
dbSNP: rs765332234
Type: single nucleotide variant
Location: chr12:47979532 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 904: a UniProt-annotated variant site (in edmmd and stl1); the 'disordered' region; the 'triple-helical region' region

Full COL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL2A1 p.Arg904Cys Pathogenic ★★ same residue
COL2A1 p.Arg904His Conflicting classifications of pathogenicity ★ ⚠ same residue
COL2A1 p.Arg904Leu Uncertain significance ★ ⚠ same residue
COL2A1 p.Arg904Pro Uncertain significance ★ ⚠ same residue
COL2A1 c.1023+1G>A Pathogenic ★★ same type
COL2A1 c.1024-2A>C Pathogenic ★★ same type
COL2A1 c.1069-2A>G Pathogenic/Likely pathogenic ★★ same type
COL2A1 c.1221+1G>A Pathogenic ★★ 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/col2a1-p-arg904 (accessed [today's date]).

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