Is COL2A1 p.Glu508fs (c.1522_1523del) pathogenic?

COL2A1 p.Glu508fs (c.15221523del) is classified Pathogenic in COL2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-24). Absent from gnomAD.

How common is COL2A1 p.Glu508fs (c.1522_1523del) in the general population?

COL2A1 p.Glu508fs (c.1522_1523del) is absent from gnomAD (gnomAD).

COL2A1 p.Glu508fs

c.1522_1523del · rs2136570754 · VCV1363808

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 23 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.2	GERP -2.8, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL2A1
Protein: p.Glu508fs
Coding: c.1522_1523del
MANE Select: NM_001844
dbSNP: rs2136570754
Type: Microsatellite
Location: chr12:47986340 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 508: 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.Glu508Gly Uncertain significance ★ ⚠ same residue
COL2A1 p.Cys1289fs Pathogenic ★★ same type
COL2A1 p.Gly1089del Pathogenic/Likely pathogenic ★★ same type
COL2A1 p.Gly1128fs Pathogenic ★★ same type
COL2A1 p.Gly993fs Pathogenic ★★ same type
COL2A1 p.1339SK[1] Uncertain significance ★★ same type
COL2A1 p.Gly186del Uncertain significance ★★ same type
COL2A1 c.1267-14_1267-12del Likely benign ★★ 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-glu508fs (accessed [today's date]).

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