Is ACAN p.Ser98fs (c.293_315del) pathogenic?

ACAN p.Ser98fs (c.293315del) is classified Likely pathogenic in ACAN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-16). Absent from gnomAD; Associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans.

How common is ACAN p.Ser98fs (c.293_315del) in the general population?

ACAN p.Ser98fs (c.293_315del) is absent from gnomAD (gnomAD).

How is Familial osteochondritis dissecans inherited?

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

ACAN p.Ser98fs

Q: What condition is associated with ACAN p.Ser98fs (c.293_315del)?

ACAN p.Ser98fs (c.293_315del) is associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (ClinVar).

c.293_315del · rs2141563800 · VCV1342158

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.3	GERP -0.48, 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: ACAN
Protein: p.Ser98fs
Coding: c.293_315del
MANE Select: NM_001369268
dbSNP: rs2141563800
Type: Deletion
Location: chr15:88838883 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 98: a disulfide bond; an α-helix; the ig-like v-type domain; the 'g1-a' 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.Trp290fs Pathogenic ★★ same condition
ACAN p.Gly946_Glu964del Uncertain significance ★★ same condition
ACAN p.Ala863fs Likely pathogenic ★ same condition
ACAN p.Glu1953fs Likely pathogenic ★ same condition
ACAN p.Glu406fs Likely pathogenic ★ same condition
ACAN p.Gly921_Asp922insTer Likely pathogenic ★ same condition
ACAN p.Ile701fs Likely pathogenic ★ same condition
ACAN p.Leu513fs Likely 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-ser98fs (accessed [today's date]).

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