How is Familial osteochondritis dissecans inherited?

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

ACAN p.Val407=

Q: Is ACAN p.Val407= (c.1221C>T) pathogenic?

ACAN p.Val407= (c.1221C>T) is classified Benign in ACAN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-09). Common (popmax 14.9%, 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.Val407= (c.1221C>T)?

ACAN p.Val407= (c.1221C>T) 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.Val407= (c.1221C>T) in the general population?

ACAN p.Val407= (c.1221C>T) is common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1221C>T · rs16942341 · VCV1206376

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 14.9%, 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	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -3.5, phastCons 0.019
Overall
CADD	1.085	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.9% African / African-American · 11,155/75,044 alleles

Filtering AF 14.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.5%

Overall 3.61% 58,300/1,614,024 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.9%	7
Middle Eastern	8.51%	12
South Asian	6.16%	16
Ashkenazi Jewishnot grpmax-eligible	4.98%	20
Remaining individualsnot grpmax-eligible	4.29%	23
Amishnot grpmax-eligible	4.17%	24
Admixed American	3.16%	32
European (non-Finnish)	2.88%	35
Finnishnot grpmax-eligible	1.45%	69
East Asian	0.0134%	7,481

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.Val407=
Coding: c.1221C>T
MANE Select: NM_001369268
dbSNP: rs16942341
Type: single nucleotide variant
Location: chr15:88845674 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB

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-val407 (accessed [today's date]).

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