Is ACOX1 p.Ser304= (c.912C>T) pathogenic?

ACOX1 p.Ser304= (c.912C>T) is classified Conflicting classifications of pathogenicity in ACOX1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-22). Ultra-rare (popmax 0.0164%, mid); Associated with peroxisomal acyl-CoA oxidase deficiency.

What condition is associated with ACOX1 p.Ser304= (c.912C>T)?

ACOX1 p.Ser304= (c.912C>T) is associated with peroxisomal acyl-CoA oxidase deficiency (ClinVar).

How common is ACOX1 p.Ser304= (c.912C>T) in the general population?

ACOX1 p.Ser304= (c.912C>T) is ultra-rare (popmax 0.0164%, mid) (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.Ser304=

c.912C>T · rs144826451 · VCV325382

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -1.1	GERP -1.6
Overall
CADD	9.991	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00434% 70/1,613,866 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.016%	6,247
European (non-Finnish)	0.00441%	22,691
African / African-American	0.00401%	24,969
Admixed American	0.00333%	29,985
Finnishnot grpmax-eligible	0.00312%	32,007

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.Ser304=
Coding: c.912C>T
MANE Select: NM_004035
dbSNP: rs144826451
Type: single nucleotide variant
Location: chr17:75953483 (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 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
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-ser304 (accessed [today's date]).

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