Is ARX p.Arg472Ter (c.1414C>T) pathogenic?

ARX p.Arg472Ter (c.1414C>T) is classified Pathogenic in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). Absent from gnomAD v4.1; Associated with X-linked lissencephaly with abnormal genitalia.

What condition is associated with ARX p.Arg472Ter (c.1414C>T)?

ARX p.Arg472Ter (c.1414C>T) is associated with X-linked lissencephaly with abnormal genitalia (ClinVar).

How common is ARX p.Arg472Ter (c.1414C>T) in the general population?

ARX p.Arg472Ter (c.1414C>T) is absent from gnomAD v4.1 (gnomAD).

ARX p.Arg472Ter

c.1414C>T · rs587783189 · VCV157746

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,202,066)

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	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (4 of 5, 34 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.6, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,202,066). 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.Arg472Ter
Coding: c.1414C>T
MANE Select: NM_139058
dbSNP: rs587783189
Type: single nucleotide variant
Location: chrX:25007145 (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.Arg332Cys Pathogenic/Likely pathogenic ★★ same condition
ARX p.Arg332Gly Pathogenic/Likely pathogenic ★★ same condition
ARX p.Arg332His Pathogenic ★★ same condition
ARX p.Glu294Ter Pathogenic ★★ same condition
ARX p.Pro353Leu Pathogenic ★★ same condition
ARX p.Ser319Ter Pathogenic/Likely pathogenic ★★ same condition
ARX p.Ala77Thr Uncertain significance ★★ ⚠ same condition
ARX p.Leu484Phe 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/arx-p-arg472ter (accessed [today's date]).

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