Is ARX p.Ala511Glu (c.1532C>A) pathogenic?

ARX p.Ala511Glu (c.1532C>A) is classified Uncertain significance in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-01). AlphaMissense: ambiguous (0.4135); Absent from gnomAD v4.1.

How common is ARX p.Ala511Glu (c.1532C>A) in the general population?

ARX p.Ala511Glu (c.1532C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARX p.Ala511Glu (c.1532C>A)?

AlphaMissense predicts ambiguous (score 0.4135) — an in-silico prediction, not a clinical call.

ARX p.Ala511Glu

c.1532C>A · rs2147318722 · VCV1310058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4135 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,177,671)

Computational evidence

Protein change
AlphaMissense	0.4135	ambiguous
REVEL	0.419	indeterminate
SaProt	LLR -8.66	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,715 bp · p 0.00019 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

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 1,177,671). 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.Ala511Glu
Coding: c.1532C>A
MANE Select: NM_139058
dbSNP: rs2147318722
Type: single nucleotide variant
Location: chrX:25004827 (GRCh38)
Structure: AlphaFold pLDDT 56.51

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

Similar variants

ARX p.Ala511= Likely benign ★★ same residue
ARX p.Ala511fs Likely pathogenic ★ 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

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-ala511glu (accessed [today's date]).

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