Is ACOX1 p.Pro248Ser (c.742C>T) pathogenic?

ACOX1 p.Pro248Ser (c.742C>T) is classified Uncertain significance in ACOX1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-20). AlphaMissense: ambiguous (0.3635); Absent from gnomAD v4.1; Associated with peroxisomal acyl-CoA oxidase deficiency.

What condition is associated with ACOX1 p.Pro248Ser (c.742C>T)?

ACOX1 p.Pro248Ser (c.742C>T) is associated with peroxisomal acyl-CoA oxidase deficiency (ClinVar).

How common is ACOX1 p.Pro248Ser (c.742C>T) in the general population?

ACOX1 p.Pro248Ser (c.742C>T) 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.Pro248Ser (c.742C>T)?

AlphaMissense predicts ambiguous (score 0.3635) — an in-silico prediction, not a clinical call.

ACOX1 p.Pro248Ser

c.742C>T · VCV4065808

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3635 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

peroxisomal acyl-CoA oxidase deficiency

Computational evidence

Protein change
AlphaMissense	0.3635	ambiguous
REVEL	0.855	moderately pathogenic-leaning
SaProt	LLR -8.68	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 29 kb · p 1.3e-14 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

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.Pro248Ser
Coding: c.742C>T
MANE Select: NM_004035
Type: single nucleotide variant
Location: chr17:75955598 (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-pro248ser (accessed [today's date]).

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