Is ACAN p.Ala2260= (c.6780T>G) pathogenic?

ACAN p.Ala2260= (c.6780T>G) is classified Benign in ACAN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-08). Common (popmax 64.1%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with osteochondritis dissecans.

What condition is associated with ACAN p.Ala2260= (c.6780T>G)?

ACAN p.Ala2260= (c.6780T>G) is associated with osteochondritis dissecans, spondyloepiphyseal dysplasia, Kimberley type, spondyloepimetaphyseal dysplasia, aggrecan type (ClinVar).

How is Osteochondritis dissecans inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

ACAN p.Ala2260=

Q: How common is ACAN p.Ala2260= (c.6780T>G) in the general population?

ACAN p.Ala2260= (c.6780T>G) is common (popmax 64.1%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6780T>G · rs698621 · VCV1188995

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 64.1%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

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 -1.7	GERP -2.8
Overall
CADD	2.863	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 64.1% European (non-Finnish) · 746,627/1,164,798 alleles

Filtering AF 64% ClinGen BA1/BS1 input FAF95, joint · FAF99 63.9%

Overall 59.9% 949,095/1,583,940 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	65.9%	2
European (non-Finnish)grpmax	64.1%	2
Ashkenazi Jewishnot grpmax-eligible	61.8%	2
Finnishnot grpmax-eligible	61%	2
Middle Eastern	59.9%	2
Remaining individualsnot grpmax-eligible	58.2%	2
Admixed American	51%	2
East Asian	43.8%	2
South Asian	42.1%	2
African / African-American	31%	3

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala2260=
Coding: c.6780T>G
MANE Select: NM_001369268
dbSNP: rs698621
Type: single nucleotide variant
Location: chr15:88859365 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 2260: the 'cs-2' region; the 'disordered' region

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

Disease context

osteochondritis dissecans — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Osteochondritis dissecans (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ACAN c.1733-2A>G Likely pathogenic ★★ same condition
ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same condition
ACAN p.Asp2419Asn Likely pathogenic ★★ same condition
ACAN p.Tyr164Ter Pathogenic ★★ same condition
ACAN p.Ala171Val Uncertain significance ★★ ⚠ same condition
ACAN p.Arg2503Gln Uncertain significance ★★ ⚠ same condition
ACAN p.Arg2503Trp Uncertain significance ★★ ⚠ same condition
ACAN p.Arg2560Trp Uncertain significance ★★ ⚠ 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-ala2260 (accessed [today's date]).

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