Is ACAN p.Val573= (c.1719A>G) pathogenic?

ACAN p.Val573= (c.1719A>G) is classified Benign in ACAN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-09). Common (popmax 10%, afr) — too common for a highly-penetrant pathogenic allele; Associated with spondyloepiphyseal dysplasia, Kimberley type.

How is Spondyloepiphyseal dysplasia, Kimberley type inherited?

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

ACAN p.Val573=

Q: What condition is associated with ACAN p.Val573= (c.1719A>G)?

ACAN p.Val573= (c.1719A>G) is associated with spondyloepiphyseal dysplasia, Kimberley type, spondyloepimetaphyseal dysplasia, aggrecan type, short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (ClinVar).

Q: How common is ACAN p.Val573= (c.1719A>G) in the general population?

ACAN p.Val573= (c.1719A>G) is common (popmax 10%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1719A>G · rs57669733 · VCV786631

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 10%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

spondyloepiphyseal dysplasia, Kimberley type

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 3.8	GERP -1.5, phastCons 1
Overall
CADD	5.248	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10% African / African-American · 7,506/75,052 alleles

Filtering AF 9.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.73%

Overall 0.533% 8,595/1,613,770 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10%	10
Remaining individualsnot grpmax-eligible	0.675%	148
Admixed American	0.605%	165
Middle Eastern	0.462%	216
South Asian	0.0275%	3,642
European (non-Finnish)	0.0213%	4,700

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.Val573=
Coding: c.1719A>G
MANE Select: NM_001369268
dbSNP: rs57669733
Type: single nucleotide variant
Location: chr15:88848025 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 573: the link 3 domain

Full ACAN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spondyloepiphyseal dysplasia, Kimberley type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: spondyloepimetaphyseal dysplasia, aggrecan type short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans

For Spondyloepiphyseal dysplasia, Kimberley type (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

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-val573 (accessed [today's date]).

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