Is ARX p.Pro447fs (c.1337dup) pathogenic?

ARX p.Pro447fs (c.1337dup) is classified Pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). Absent from gnomAD; Associated with X-linked lissencephaly with abnormal genitalia.

What condition is associated with ARX p.Pro447fs (c.1337dup)?

ARX p.Pro447fs (c.1337dup) is associated with X-linked lissencephaly with abnormal genitalia (ClinVar).

How common is ARX p.Pro447fs (c.1337dup) in the general population?

ARX p.Pro447fs (c.1337dup) is absent from gnomAD (gnomAD).

ARX p.Pro447fs

c.1337dup · rs797045291 · VCV210319

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked lissencephaly with abnormal genitalia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.59	GERP 0.15, phastCons 1
Region caveats
Repeat context	tandem	(GCG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Pro447fs
Coding: c.1337dup
MANE Select: NM_139058
dbSNP: rs797045291
Type: Duplication
Location: chrX:25007221 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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

Disease context

X-linked lissencephaly with abnormal genitalia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARX p.Gly397fs Pathogenic/Likely pathogenic ★★ same condition
ARX c.1120-82_1469dup Pathogenic ★ same condition
ARX c.1449-82_1469dup Pathogenic ★ same condition
ARX p.Ala275fs Likely pathogenic ★ same condition
ARX p.Glu137fs Pathogenic ★ same condition
ARX p.Gly143_Ala154dup Likely pathogenic ★ same condition
ARX p.Leu324fs Pathogenic ★ same condition
ARX p.Pro187fs Pathogenic ★ 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/arx-p-pro447fs (accessed [today's date]).

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