Is ARX p.Lys261Glu (c.781A>G) pathogenic?

ARX p.Lys261Glu (c.781A>G) is classified Uncertain significance in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: likely benign (0.2823); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARX p.Lys261Glu (c.781A>G)?

ARX p.Lys261Glu (c.781A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARX p.Lys261Glu (c.781A>G) in the general population?

ARX p.Lys261Glu (c.781A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Lys261Glu (c.781A>G)?

AlphaMissense predicts likely benign (score 0.2823) — an in-silico prediction, not a clinical call.

ARX p.Lys261Glu

c.781A>G · rs1046097289 · VCV2314704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2823 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2823	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -4.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.39, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,633 bp · p 0.032 · regional, not allelic
Overall
CADD	19.95	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: ARX
Protein: p.Lys261Glu
Coding: c.781A>G
MANE Select: NM_139058
dbSNP: rs1046097289
Type: single nucleotide variant
Location: chrX:25013214 (GRCh38)
Structure: AlphaFold pLDDT 56.51

Full ARX 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

ARX p.Glu308Ter Pathogenic ★★ same condition
ARX c.196+6G>A Uncertain significance ★★ same condition
ARX p.Ala149Val Uncertain significance ★★ ⚠ same condition
ARX p.Arg204Cys Uncertain significance ★★ ⚠ same condition
ARX p.Gly34Ala Uncertain significance ★★ ⚠ same condition
ARX p.Leu159Phe Uncertain significance ★★ ⚠ same condition
ARX p.Pro135Leu Uncertain significance ★★ ⚠ same condition
ARX p.Ser31Arg 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-lys261glu (accessed [today's date]).

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