Is ARX p.Pro130Gln (c.389C>A) pathogenic?

ARX p.Pro130Gln (c.389C>A) is classified Likely benign in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-29). AlphaMissense: likely benign (0.1206); Ultra-rare (popmax 0.0153%, eas).

How common is ARX p.Pro130Gln (c.389C>A) in the general population?

ARX p.Pro130Gln (c.389C>A) is ultra-rare (popmax 0.0153%, eas) (gnomAD).

What do computational predictors say about ARX p.Pro130Gln (c.389C>A)?

AlphaMissense predicts likely benign (score 0.1206) — an in-silico prediction, not a clinical call.

ARX p.Pro130Gln

c.389C>A · rs1064795129 · VCV421425

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1206 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1206	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -12.95	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.71	GERP -1.3, phastCons 0.95
Regional constraint	o/e 0.87	unconstrained · MANE · 2,633 bp · p 0.032 · regional, not allelic
Overall
CADD	19.08	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

Grpmax group 0.0153% East Asian · 1/6,543 alleles

Overall 0.000311% 2/643,822 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0153%	6,543
Remaining individualsnot grpmax-eligible	0.00438%	22,821

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ARX
Protein: p.Pro130Gln
Coding: c.389C>A
MANE Select: NM_139058
dbSNP: rs1064795129
Type: single nucleotide variant
Location: chrX:25013606 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 130: the 'disordered' region

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

Similar variants

ARX p.Pro130Leu Uncertain significance ★ ⚠ same residue
ARX p.Pro130Thr Uncertain significance ★ ⚠ same residue
ARX p.Pro130= Likely benign ★ 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

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-pro130gln (accessed [today's date]).

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