Is AOX1 p.Pro23Arg (c.68C>G) pathogenic?

AOX1 p.Pro23Arg (c.68C>G) is classified Uncertain significance in AOX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely pathogenic (0.653); Absent from gnomAD v4.1.

How common is AOX1 p.Pro23Arg (c.68C>G) in the general population?

AOX1 p.Pro23Arg (c.68C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AOX1 p.Pro23Arg (c.68C>G)?

AlphaMissense predicts likely pathogenic (score 0.653) — an in-silico prediction, not a clinical call.

AOX1 p.Pro23Arg

c.68C>G · VCV4113978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.653	likely pathogenic
REVEL	0.485	indeterminate
SaProt	LLR -16.03	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.2	GERP 2.4, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 85 kb · p 0.85 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: AOX1
Protein: p.Pro23Arg
Coding: c.68C>G
MANE Select: NM_001159
Type: single nucleotide variant
Location: chr2:200593168 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.13 · 8 PDB
Residue 23: the 2fe-2s ferredoxin-type domain

Full AOX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AOX1 p.Ala1083Gly Benign ★★ same type
AOX1 p.Arg130= Benign ★★ same type
AOX1 p.Gln314Arg Benign ★★ same type
AOX1 p.Gln737= Benign ★★ same type
AOX1 p.Ile598Asn Benign ★★ same type
AOX1 p.Leu553= Benign ★★ same type
AOX1 p.Pro1245= Benign ★★ same type
AOX1 p.Pro702= Likely benign ★★ 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/aox1-p-pro23arg (accessed [today's date]).

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