Is ACAN p.Arg173fs (c.517_530del) pathogenic?

ACAN p.Arg173fs (c.517530del) is classified Likely pathogenic in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). Associated with ACAN-related disorder.

What condition is associated with ACAN p.Arg173fs (c.517_530del)?

ACAN p.Arg173fs (c.517_530del) is associated with ACAN-related disorder (ClinVar).

ACAN p.Arg173fs

c.517_530del · VCV4292833

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ACAN-related disorder

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 4 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: ACAN
Protein: p.Arg173fs
Coding: c.517_530del
MANE Select: NM_001369268
Type: Deletion
Location: chr15:88840074 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 173: an α-helix; the link 1 domain; the 'g1-b' region

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

Disease context

ACAN-related disorder

Similar variants

ACAN p.Asn108fs Pathogenic/Likely pathogenic ★★ same condition
ACAN p.Arg173Trp Uncertain significance ★★ ⚠ same residue
ACAN p.Arg173= Likely benign ★★ same residue
ACAN p.Ala2139fs Likely pathogenic ★ same condition
ACAN p.Asp865fs Pathogenic ★ same condition
ACAN p.Gln1618fs Pathogenic ★ same condition
ACAN p.Gly998fs Pathogenic ★ same condition
ACAN p.Ile424fs Pathogenic ★ same condition

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/acan-p-arg173fs (accessed [today's date]).

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