Is ACAN p.Val705fs (c.2112dup) pathogenic?

ACAN p.Val705fs (c.2112dup) is classified Pathogenic in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). Associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans.

How is Familial osteochondritis dissecans inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ACAN p.Val705fs

Q: What condition is associated with ACAN p.Val705fs (c.2112dup)?

ACAN p.Val705fs (c.2112dup) is associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (ClinVar).

c.2112dup · VCV3342274

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans

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 11 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 1.6

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

Variant & gene context

Gene: ACAN
Protein: p.Val705fs
Coding: c.2112dup
MANE Select: NM_001369268
Type: Duplication
Location: chr15:88851877 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 705: the 'ks' region

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

Disease context

short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial osteochondritis dissecans (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

ACAN p.Gly366_Glu367insTer Pathogenic ★★ same condition
ACAN p.Ala2277fs Likely pathogenic ★ same condition
ACAN p.Arg668fs Pathogenic ★ same condition
ACAN p.Asp953fs Likely pathogenic ★ same condition
ACAN p.Gly554fs Likely pathogenic ★ same condition
ACAN p.Pro510_Glu511insAlaCysLeuArgThrGlyAlaValIleAlaSerPro Uncertain significance ★ same condition
ACAN p.Val705Gly Uncertain significance ★ ⚠ same residue
ACAN p.Val705= Likely benign ★ same residue

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-val705fs (accessed [today's date]).

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