Is COL2A1 p.Ala353fs (c.1056del) pathogenic?

COL2A1 p.Ala353fs (c.1056del) is classified Pathogenic in COL2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-10-30). Absent from gnomAD.

How common is COL2A1 p.Ala353fs (c.1056del) in the general population?

COL2A1 p.Ala353fs (c.1056del) is absent from gnomAD (gnomAD).

COL2A1 p.Ala353fs

c.1056del · rs794727185 · VCV194728

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 17 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1

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.Ala353fs
Coding: c.1056del
MANE Select: NM_001844
dbSNP: rs794727185
Type: Deletion
Location: chr12:47989773 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 353: 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.Ala353Ser Uncertain significance ★★ ⚠ same residue
COL2A1 p.Ala353Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
COL2A1 c.1023+3_1023+6del Pathogenic/Likely pathogenic ★★ same type
COL2A1 c.610-17_617del Pathogenic/Likely pathogenic ★★ same type
COL2A1 c.906_924+9del Pathogenic/Likely pathogenic ★★ same type
COL2A1 p.1205PGP[2] Pathogenic ★★ same type
COL2A1 p.722PGT[1] Pathogenic/Likely pathogenic ★★ same type
COL2A1 p.Asp1234fs 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-ala353fs (accessed [today's date]).

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