Is ACOX1 p.Asp243Glu (c.729C>G) pathogenic?

ACOX1 p.Asp243Glu (c.729C>G) is classified Uncertain significance in ACOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.1246); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACOX1 p.Asp243Glu (c.729C>G)?

ACOX1 p.Asp243Glu (c.729C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ACOX1 p.Asp243Glu (c.729C>G) in the general population?

ACOX1 p.Asp243Glu (c.729C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACOX1 p.Asp243Glu (c.729C>G)?

AlphaMissense predicts likely benign (score 0.1246) — an in-silico prediction, not a clinical call.

ACOX1 p.Asp243Glu

c.729C>G · VCV4217140

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1246 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1246	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 29 kb · p 1.3e-14 · regional, not allelic
Overall
CADD	18.76	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Asp243Glu
Coding: c.729C>G
MANE Select: NM_004035
Type: single nucleotide variant
Location: chr17:75955611 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ACOX1 p.Asp243= Uncertain significance same residue
ACOX1 p.Ala296Val Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala346Val Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala375Thr Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala499Ser Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala553Thr Uncertain significance ★★ ⚠ same condition
ACOX1 p.Ala571Val Uncertain significance ★★ ⚠ same condition
ACOX1 p.Arg122His Uncertain significance ★★ 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-asp243glu (accessed [today's date]).

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