Is ACAN p.Ser930Ile (c.2789G>T) pathogenic?

ACAN p.Ser930Ile (c.2789G>T) is classified Benign in ACAN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-08). AlphaMissense: likely benign (0.1852); Common (popmax 64.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with osteochondritis dissecans.

What condition is associated with ACAN p.Ser930Ile (c.2789G>T)?

ACAN p.Ser930Ile (c.2789G>T) 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.

What do computational predictors say about ACAN p.Ser930Ile (c.2789G>T)?

AlphaMissense predicts likely benign (score 0.1852) — an in-silico prediction, not a clinical call.

ACAN p.Ser930Ile

Q: How common is ACAN p.Ser930Ile (c.2789G>T) in the general population?

ACAN p.Ser930Ile (c.2789G>T) is common (popmax 64.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2789G>T · rs938608 · VCV1188886

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1852 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 64.6%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

osteochondritis dissecans

Computational evidence

Protein change
AlphaMissense	0.1852	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -9.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -2.7
Regional constraint	o/e 1.00	unconstrained · MANE · 19 kb · p 0.97 · regional, not allelic
Overall
CADD	7.408	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 64.6% European (non-Finnish) · 761,811/1,179,086 alleles

Filtering AF 64.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.4%

Overall 60.2% 971,002/1,612,482 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	65.7%	2
European (non-Finnish)grpmax	64.6%	2
Ashkenazi Jewishnot grpmax-eligible	61.1%	2
Middle Eastern	59.1%	2
Finnishnot grpmax-eligible	58.8%	2
Remaining individualsnot grpmax-eligible	58.3%	2
South Asian	50.5%	2
African / African-American	47.4%	2
Admixed American	36.8%	3
East Asian	21.2%	5

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.Ser930Ile
Coding: c.2789G>T
MANE Select: NM_001369268
dbSNP: rs938608
Type: single nucleotide variant
Location: chr15:88855374 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.32 · 4 PDB
Residue 930: a UniProt-annotated variant site (in); the 'disordered' region; the 'cs-1' 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 short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans

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 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-ser930ile (accessed [today's date]).

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