Is ACOX1 p.Ser568fs (c.1704_1707del) pathogenic?

ACOX1 p.Ser568fs (c.17041707del) is classified Pathogenic/Likely pathogenic in ACOX1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-18). Very rare (popmax 0.000508%, nfe); Associated with peroxisomal acyl-CoA oxidase deficiency.

What condition is associated with ACOX1 p.Ser568fs (c.1704_1707del)?

ACOX1 p.Ser568fs (c.1704_1707del) is associated with peroxisomal acyl-CoA oxidase deficiency, Mitchell syndrome (ClinVar).

How common is ACOX1 p.Ser568fs (c.1704_1707del) in the general population?

ACOX1 p.Ser568fs (c.1704_1707del) is very rare (popmax 0.000508%, nfe) (gnomAD).

How is Peroxisomal acyl-CoA oxidase deficiency inherited?

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

ACOX1 p.Ser568fs

c.1704_1707del · rs1332660959 · VCV1459402

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Conditions

peroxisomal acyl-CoA oxidase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.43, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,040 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,878 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	0.000508%	196,673

Remaining individuals 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: ACOX1
Protein: p.Ser568fs
Coding: c.1704_1707del
MANE Select: NM_004035
dbSNP: rs1332660959
Type: Microsatellite
Location: chr17:75949238 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.95

Full ACOX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisomal acyl-CoA oxidase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Mitchell syndrome

For Peroxisomal acyl-CoA oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

ACOX1 p.Leu596_Thr597insTer Pathogenic/Likely pathogenic ★★ same condition
ACOX1 p.Glu140fs Likely pathogenic ★ same condition
ACOX1 p.Lys73del Uncertain significance ★ same condition
ACOX1 c.1584+16_1584+19del Likely benign ★ same condition
ACOX1 c.1935+14_1935+15del Likely benign ★ same condition
ACOX1 c.1936-20_1936-18del Likely benign ★ same condition
ACOX1 c.1729-2del Likely pathogenic ★★ same condition
ACOX1 c.538+1G>A 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/acox1-p-ser568fs (accessed [today's date]).

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