Is ACOX1 p.Asp440= (c.1320T>C) pathogenic?

ACOX1 p.Asp440= (c.1320T>C) is classified Benign in ACOX1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 21.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with peroxisomal acyl-CoA oxidase deficiency.

What condition is associated with ACOX1 p.Asp440= (c.1320T>C)?

ACOX1 p.Asp440= (c.1320T>C) is associated with peroxisomal acyl-CoA oxidase deficiency (ClinVar).

How is Peroxisomal acyl-CoA oxidase deficiency inherited?

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

ACOX1 p.Asp440=

Q: How common is ACOX1 p.Asp440= (c.1320T>C) in the general population?

ACOX1 p.Asp440= (c.1320T>C) is common (popmax 21.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1320T>C · rs8065946 · VCV259220

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 21.4%, afr) — too common for a highly-penetrant pathogenic allele

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 1.2	GERP -1.6, phastCons 1
Overall
CADD	7.513	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.4% African / African-American · 16,025/74,986 alleles

Filtering AF 21.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 21%

Overall 1.43% 23,031/1,614,130 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.4%	5
Middle Eastern	3.45%	29
Ashkenazi Jewishnot grpmax-eligible	3.43%	29
Remaining individualsnot grpmax-eligible	2.34%	43
Admixed American	2.32%	43
South Asian	0.361%	277
European (non-Finnish)	0.22%	454
East Asian	0.00446%	22,444

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.Asp440=
Coding: c.1320T>C
MANE Select: NM_004035
dbSNP: rs8065946
Type: single nucleotide variant
Location: chr17:75949876 (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.Asp440Asn Uncertain significance ★ ⚠ 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-asp440 (accessed [today's date]).

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