Is ACAN p.Thr62= (c.186C>T) pathogenic?

ACAN p.Thr62= (c.186C>T) is classified Benign/Likely benign in ACAN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Rare (popmax 0.951%, afr); Associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans.

What condition is associated with ACAN p.Thr62= (c.186C>T)?

ACAN p.Thr62= (c.186C>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).

How common is ACAN p.Thr62= (c.186C>T) in the general population?

ACAN p.Thr62= (c.186C>T) is rare (popmax 0.951%, afr) (gnomAD).

How is Familial osteochondritis dissecans inherited?

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

ACAN p.Thr62=

c.186C>T · rs191648646 · VCV287638

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.951%, 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 -3.6	GERP -3.5
Overall
CADD	7.639	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.951% African / African-American · 714/75,052 alleles

Filtering AF 0.893% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.87%

Overall 0.0561% 906/1,613,966 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.951%	105
Admixed American	0.157%	639
Remaining individualsnot grpmax-eligible	0.101%	992
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
European (non-Finnish)	0.00254%	39,329
South Asian	0.0022%	45,536

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.Thr62=
Coding: c.186C>T
MANE Select: NM_001369268
dbSNP: rs191648646
Type: single nucleotide variant
Location: chr15:88838778 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 62: a disulfide bond; 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

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

For Familial osteochondritis dissecans (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

ACAN p.Thr62Asn Conflicting classifications of pathogenicity ★ ⚠ 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
ACAN p.Lys74Ter 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-thr62 (accessed [today's date]).

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