Is ACOX1 p.Leu596= (c.1788C>T) pathogenic?

ACOX1 p.Leu596= (c.1788C>T) is classified Likely benign in ACOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). Very rare (popmax 0.00223%, eas); Associated with peroxisomal acyl-CoA oxidase deficiency.

What condition is associated with ACOX1 p.Leu596= (c.1788C>T)?

ACOX1 p.Leu596= (c.1788C>T) is associated with peroxisomal acyl-CoA oxidase deficiency (ClinVar).

How common is ACOX1 p.Leu596= (c.1788C>T) in the general population?

ACOX1 p.Leu596= (c.1788C>T) is very rare (popmax 0.00223%, eas) (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.Leu596=

c.1788C>T · rs1397533330 · VCV1590998

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

peroxisomal acyl-CoA oxidase deficiency

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 1.6	GERP -3.4, phastCons 1
Overall
CADD	8.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 0.000205% 3/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
Admixed American	0.00167%	60,004
European (non-Finnish)	8.47e-05%	1,180,027

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.Leu596=
Coding: c.1788C>T
MANE Select: NM_004035
dbSNP: rs1397533330
Type: single nucleotide variant
Location: chr17:75948398 (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

For Peroxisomal acyl-CoA oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

ACOX1 p.Leu596_Thr597insTer Pathogenic/Likely pathogenic ★★ same residue
ACOX1 c.538+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACOX1 c.945-1G>C Likely pathogenic ★★ same condition
ACOX1 p.Arg148Ter Pathogenic ★★ same condition
ACOX1 p.Arg302Ter Pathogenic ★★ same condition
ACOX1 p.Arg94Ter Pathogenic ★★ same condition
ACOX1 p.Asn237Ser Pathogenic/Likely pathogenic ★★ same condition
ACOX1 p.Gln114Ter 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-leu596 (accessed [today's date]).

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