Is ARX p.Lys17Arg (c.50A>G) pathogenic?

ARX p.Lys17Arg (c.50A>G) is classified Uncertain significance in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.1347); Absent from gnomAD v4.1.

How common is ARX p.Lys17Arg (c.50A>G) in the general population?

ARX p.Lys17Arg (c.50A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Lys17Arg (c.50A>G)?

AlphaMissense predicts likely benign (score 0.1347) — an in-silico prediction, not a clinical call.

ARX p.Lys17Arg

c.50A>G · rs2519109298 · VCV2501414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1347 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1347	likely benign
REVEL	0.385	indeterminate
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,633 bp · p 0.032 · regional, not allelic
Overall
CADD	24.3	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.Lys17Arg
Coding: c.50A>G
MANE Select: NM_139058
dbSNP: rs2519109298
Type: single nucleotide variant
Location: chrX:25015688 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 17: the 'disordered' region

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

Similar variants

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
ARX p.Cys10Ter 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-lys17arg (accessed [today's date]).

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