Is ACAN p.Tyr2003= (c.6009T>C) pathogenic?

ACAN p.Tyr2003= (c.6009T>C) is classified Benign/Likely benign in ACAN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-11). Low-frequency (popmax 4.06%, afr); Associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans.

How common is ACAN p.Tyr2003= (c.6009T>C) in the general population?

ACAN p.Tyr2003= (c.6009T>C) is low-frequency (popmax 4.06%, afr) (gnomAD).

How is Familial osteochondritis dissecans inherited?

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

ACAN p.Tyr2003=

Q: What condition is associated with ACAN p.Tyr2003= (c.6009T>C)?

ACAN p.Tyr2003= (c.6009T>C) is associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans, spondyloepiphyseal dysplasia, Kimberley type, spondyloepimetaphyseal dysplasia, aggrecan type (ClinVar).

c.6009T>C · rs35676128 · VCV768723

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.06%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.55, phastCons 1
Overall
CADD	1.645	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.06% African / African-American · 3,046/75,028 alleles

Filtering AF 3.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.89%

Overall 0.454% 7,326/1,613,860 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.06%	25
Admixed American	2.05%	49
Middle Eastern	1.52%	66
East Asian	1.45%	69
Remaining individualsnot grpmax-eligible	0.981%	102
Ashkenazi Jewishnot grpmax-eligible	0.557%	179
South Asian	0.347%	288
Finnishnot grpmax-eligible	0.102%	983
European (non-Finnish)	0.0976%	1,025

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ACAN
Protein: p.Tyr2003=
Coding: c.6009T>C
MANE Select: NM_001369268
dbSNP: rs35676128
Type: single nucleotide variant
Location: chr15:88858594 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 2003: the 'cs-2' 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

Also linked: spondyloepiphyseal dysplasia, Kimberley type spondyloepimetaphyseal dysplasia, aggrecan type

For Familial osteochondritis dissecans (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

ACAN c.1733-2A>G Likely pathogenic ★★ same condition
ACAN c.7302+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACAN p.Arg236Ter Pathogenic ★★ same condition
ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same condition
ACAN p.Asp2419Asn Likely pathogenic ★★ same condition
ACAN p.Glu254Ter Pathogenic ★★ same condition
ACAN p.Lys74Ter Pathogenic ★★ same condition
ACAN p.Trp377Ter Pathogenic/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-tyr2003 (accessed [today's date]).

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