Is COL2A1 p.Gly5= (c.15G>A) pathogenic?

COL2A1 p.Gly5= (c.15G>A) is classified Benign in COL2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). Very rare (popmax 0.00245%, eas).

How common is COL2A1 p.Gly5= (c.15G>A) in the general population?

COL2A1 p.Gly5= (c.15G>A) is very rare (popmax 0.00245%, eas) (gnomAD).

COL2A1 p.Gly5=

c.15G>A · rs746800217 · VCV2778314

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00245%, 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 3.9	GERP 0.025, phastCons 1
Overall
CADD	13.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00245% East Asian · 1/40,872 alleles

Overall 7.16e-05% 1/1,396,750 alleles · very rare

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.Gly5=
Coding: c.15G>A
MANE Select: NM_001844
dbSNP: rs746800217
Type: single nucleotide variant
Location: chr12:48004307 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB

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

Similar variants

COL2A1 p.Gly5Arg Uncertain significance ★★ ⚠ same residue
COL2A1 p.Gly5Ala Conflicting classifications of pathogenicity ★ ⚠ 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
COL2A1 c.1222-2A>G Pathogenic ★★ same type
COL2A1 c.1365+1G>A Pathogenic/Likely 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-gly5 (accessed [today's date]).

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