Is ACOX2 p.Cys434= (c.1302T>C) pathogenic?

ACOX2 p.Cys434= (c.1302T>C) is classified Benign in ACOX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Common (popmax 63.5%, afr) — too common for a highly-penetrant pathogenic allele.

ACOX2 p.Cys434=

Q: How common is ACOX2 p.Cys434= (c.1302T>C) in the general population?

ACOX2 p.Cys434= (c.1302T>C) is common (popmax 63.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1302T>C · rs1127745 · VCV1600142

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 63.5%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.36	GERP -3.3, phastCons 0.006
Overall
CADD	6.769	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 63.5% African / African-American · 47,603/74,970 alleles

Filtering AF 63% ClinGen BA1/BS1 input FAF95, joint · FAF99 62.8%

Overall 12.5% 201,889/1,613,910 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	63.5%	2
Middle Eastern	22.5%	4
East Asian	21.3%	5
Ashkenazi Jewishnot grpmax-eligible	16.1%	6
Remaining individualsnot grpmax-eligible	14.6%	7
Admixed American	13.6%	7
South Asian	11.2%	9
Amishnot grpmax-eligible	9.56%	10
European (non-Finnish)	9.03%	11
Finnishnot grpmax-eligible	7.18%	14

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: ACOX2
Protein: p.Cys434=
Coding: c.1302T>C
MANE Select: NM_003500
dbSNP: rs1127745
Type: single nucleotide variant
Location: chr3:58526510 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.49
Residue 434: 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

Similar variants

ACOX2 p.Ala106Val Uncertain significance ★★ ⚠ same type
ACOX2 p.Ala48Glu Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg197Gln Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg197Trp Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg215Trp Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg318His Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg323Cys Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg323His Uncertain significance ★★ ⚠ same type

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-cys434 (accessed [today's date]).

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