Is ACOX1 p.Arg9Gly (c.25C>G) pathogenic?

ACOX1 p.Arg9Gly (c.25C>G) is classified Uncertain significance in ACOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-14). AlphaMissense: likely pathogenic (0.9436); Absent from gnomAD v4.1; Associated with peroxisomal acyl-CoA oxidase deficiency.

What condition is associated with ACOX1 p.Arg9Gly (c.25C>G)?

ACOX1 p.Arg9Gly (c.25C>G) is associated with peroxisomal acyl-CoA oxidase deficiency (ClinVar).

How common is ACOX1 p.Arg9Gly (c.25C>G) in the general population?

ACOX1 p.Arg9Gly (c.25C>G) is absent from gnomAD v4.1 (gnomAD).

How is Peroxisomal acyl-CoA oxidase deficiency inherited?

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

What do computational predictors say about ACOX1 p.Arg9Gly (c.25C>G)?

AlphaMissense predicts likely pathogenic (score 0.9436) — an in-silico prediction, not a clinical call.

ACOX1 p.Arg9Gly

c.25C>G · rs765997588 · VCV2956247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9436 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

peroxisomal acyl-CoA oxidase deficiency

Computational evidence

Protein change
AlphaMissense	0.9436	likely pathogenic
REVEL	0.559	indeterminate
SaProt	LLR -12.68	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 29 kb · p 1.3e-14 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACOX1
Protein: p.Arg9Gly
Coding: c.25C>G
MANE Select: NM_004035
dbSNP: rs765997588
Type: single nucleotide variant
Location: chr17:75979049 (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.Arg9= Likely benign ★ 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-arg9gly (accessed [today's date]).

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