Is ACOX2 p.Ala665= (c.1995C>T) pathogenic?

ACOX2 p.Ala665= (c.1995C>T) is classified Likely benign in ACOX2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-25). Absent from gnomAD v4.1; Associated with ACOX2-related disorder.

What condition is associated with ACOX2 p.Ala665= (c.1995C>T)?

ACOX2 p.Ala665= (c.1995C>T) is associated with ACOX2-related disorder (ClinVar).

How common is ACOX2 p.Ala665= (c.1995C>T) in the general population?

ACOX2 p.Ala665= (c.1995C>T) is absent from gnomAD v4.1 (gnomAD).

ACOX2 p.Ala665=

c.1995C>T · rs2471437232 · VCV3046987

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ACOX2-related disorder

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 4	GERP 1.2, phastCons 1
Overall
CADD	9.592	PHRED · no single calibrated threshold — expert panels disagree

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: ACOX2
Protein: p.Ala665=
Coding: c.1995C>T
MANE Select: NM_003500
dbSNP: rs2471437232
Type: single nucleotide variant
Location: chr3:58505275 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.49
Residue 665: a UniProt-annotated variant site (in cbas6; patient liver samples show absence of the protein; complete loss of fatty acid beta-oxidation activity)

Full ACOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACOX2-related disorder

Similar variants

ACOX2 p.Ala665Asp Uncertain significance ★ ⚠ same residue
ACOX2 p.Arg329Gln Uncertain significance ★★ ⚠ same condition
ACOX2 p.Gln146Ter Uncertain significance ★ same condition
ACOX2 p.Ala395Val Uncertain significance ⚠ same condition
ACOX2 p.Lys512Asn Uncertain significance ⚠ same condition
ACOX2 p.Thr465Met Uncertain significance ⚠ same condition
ACOX2 p.Val8Glu Uncertain significance ⚠ same condition
ACOX2 c.1156-3C>T Likely benign 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/acox2-p-ala665 (accessed [today's date]).

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