How is Familial osteochondritis dissecans inherited?

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

ACAN p.Pro510=

Q: Is ACAN p.Pro510= (c.1530G>A) pathogenic?

ACAN p.Pro510= (c.1530G>A) is classified Benign in ACAN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-09). Common (popmax 9.96%, afr) — too common for a highly-penetrant pathogenic allele; Associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans.

Q: What condition is associated with ACAN p.Pro510= (c.1530G>A)?

ACAN p.Pro510= (c.1530G>A) 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).

Q: How common is ACAN p.Pro510= (c.1530G>A) in the general population?

ACAN p.Pro510= (c.1530G>A) is common (popmax 9.96%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1530G>A · rs34637731 · VCV284338

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 9.96%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.7
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.96% African / African-American · 7,415/74,412 alleles

Filtering AF 9.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.7%

Overall 0.535% 8,492/1,585,858 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.96%	10
Remaining individualsnot grpmax-eligible	0.696%	144
Admixed American	0.611%	164
Middle Eastern	0.475%	211
South Asian	0.0301%	3,326
European (non-Finnish)	0.0213%	4,687
East Asian	0.00921%	10,862

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.Pro510=
Coding: c.1530G>A
MANE Select: NM_001369268
dbSNP: rs34637731
Type: single nucleotide variant
Location: chr15:88847343 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 510: a disulfide bond; the link 3 domain; the 'g2-b' 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 p.Pro510_Glu511insAlaCysLeuArgThrGlyAlaValIleAlaSerPro Uncertain significance ★ same residue
ACAN p.Pro510Leu Uncertain significance ★ ⚠ same residue
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

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-pro510 (accessed [today's date]).

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