Is ACOX1 p.Phe434= (c.1302C>T) pathogenic?

ACOX1 p.Phe434= (c.1302C>T) is classified Benign/Likely benign in ACOX1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 1.4%, afr); Associated with peroxisomal acyl-CoA oxidase deficiency.

What condition is associated with ACOX1 p.Phe434= (c.1302C>T)?

ACOX1 p.Phe434= (c.1302C>T) is associated with peroxisomal acyl-CoA oxidase deficiency (ClinVar).

How common is ACOX1 p.Phe434= (c.1302C>T) in the general population?

ACOX1 p.Phe434= (c.1302C>T) is low-frequency (popmax 1.4%, afr) (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.Phe434=

c.1302C>T · rs144742319 · VCV712810

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.4%, afr)

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 3.7	GERP -0.46, phastCons 1
Overall
CADD	10.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.4% African / African-American · 1,047/75,042 alleles

Filtering AF 1.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3%

Overall 0.0705% 1,138/1,614,150 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.4%	72
Middle Eastern	0.149%	673
Remaining individualsnot grpmax-eligible	0.0752%	1,330
Admixed American	0.0433%	2,308
South Asian	0.0011%	91,076
European (non-Finnish)	0.000678%	147,505

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.Phe434=
Coding: c.1302C>T
MANE Select: NM_004035
dbSNP: rs144742319
Type: single nucleotide variant
Location: chr17:75949894 (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

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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
ACOX1 p.Glu84Ter 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-phe434 (accessed [today's date]).

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