Is ARX p.Arg345Gln (c.1034G>A) pathogenic?

ARX p.Arg345Gln (c.1034G>A) is classified Uncertain significance in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely pathogenic (0.8898); Absent from gnomAD v4.1.

How common is ARX p.Arg345Gln (c.1034G>A) in the general population?

ARX p.Arg345Gln (c.1034G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Arg345Gln (c.1034G>A)?

AlphaMissense predicts likely pathogenic (score 0.8898) — an in-silico prediction, not a clinical call.

ARX p.Arg345Gln

c.1034G>A · VCV4532377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8898 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,205,443)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8898	likely pathogenic
REVEL	0.681	pathogenic-leaning
SaProt	LLR -12.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 0.023, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 5,714 bp · p 1e-11 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,205,443). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARX
Protein: p.Arg345Gln
Coding: c.1034G>A
MANE Select: NM_139058
Type: single nucleotide variant
Location: chrX:25012961 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 345: a DNA-binding region

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

Similar variants

ARX p.Arg345= Uncertain significance ★ same residue
ARX p.Arg330His Likely pathogenic ★★ same type
ARX p.Arg332Cys Pathogenic/Likely pathogenic ★★ same type
ARX p.Arg332Gly Pathogenic/Likely pathogenic ★★ same type
ARX p.Arg332His Pathogenic ★★ same type
ARX p.Arg371Gln Likely pathogenic ★★ same type
ARX p.Arg371Ter Pathogenic ★★ same type
ARX p.Arg384Cys Pathogenic/Likely pathogenic ★★ 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/arx-p-arg345gln (accessed [today's date]).

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