Is ACAN p.Ala679= (c.2037G>A) pathogenic?

ACAN p.Ala679= (c.2037G>A) is classified Benign in ACAN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-16). Rare (popmax 0.375%, sas); Associated with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans.

How common is ACAN p.Ala679= (c.2037G>A) in the general population?

ACAN p.Ala679= (c.2037G>A) is rare (popmax 0.375%, sas) (gnomAD).

How is Familial osteochondritis dissecans inherited?

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

ACAN p.Ala679=

Q: What condition is associated with ACAN p.Ala679= (c.2037G>A)?

ACAN p.Ala679= (c.2037G>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).

c.2037G>A · rs372553119 · VCV283926

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.375%, sas)

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 -2.7	GERP -3.1
Overall
CADD	1.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.375% South Asian · 329/87,838 alleles

Filtering AF 0.341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.328%

Overall 0.0351% 560/1,595,386 alleles · rare exomes 526/1,443,102 · genomes 34/152,284 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.375%	267
Middle Eastern	0.282%	355
Remaining individualsnot grpmax-eligible	0.0629%	1,589
European (non-Finnish)	0.0137%	7,318
African / African-American	0.0134%	7,464
East Asian	0.00681%	14,685
Admixed American	0.00351%	28,461

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.Ala679=
Coding: c.2037G>A
MANE Select: NM_001369268
dbSNP: rs372553119
Type: single nucleotide variant
Location: chr15:88851804 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 679: the 'ks' 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.Ala679Val 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
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-ala679 (accessed [today's date]).

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