Is ARX p.Pro187= (c.561C>G) pathogenic?

ARX p.Pro187= (c.561C>G) is classified Likely benign in ARX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-07). Very rare (popmax 0.000132%, nfe); Associated with intellectual disability, X-linked, with or without seizures, ARX-related.

How common is ARX p.Pro187= (c.561C>G) in the general population?

ARX p.Pro187= (c.561C>G) is very rare (popmax 0.000132%, nfe) (gnomAD).

ARX p.Pro187=

Q: What condition is associated with ARX p.Pro187= (c.561C>G)?

ARX p.Pro187= (c.561C>G) is associated with intellectual disability, X-linked, with or without seizures, ARX-related, developmental and epileptic encephalopathy, 1 (ClinVar).

c.561C>G · rs1396204461 · VCV2940653

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000132%, nfe)

Conditions

intellectual disability, X-linked, with or without seizures, ARX-related

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP 0.57, phastCons 1
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000132% European (non-Finnish) · 1/757,275 alleles

Overall 0.000121% 1/828,939 alleles · very rare

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.Pro187=
Coding: c.561C>G
MANE Select: NM_139058
dbSNP: rs1396204461
Type: single nucleotide variant
Location: chrX:25013434 (GRCh38)
Structure: AlphaFold pLDDT 56.51
Residue 187: the 'disordered' region

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

Disease context

intellectual disability, X-linked, with or without seizures, ARX-related — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 1

Similar variants

ARX p.Pro187dup Uncertain significance ★★ same residue
ARX p.Arg330His Likely pathogenic ★★ same condition
ARX p.Arg332Gly Pathogenic/Likely pathogenic ★★ same condition
ARX p.Arg332His Pathogenic ★★ same condition
ARX p.Arg371Gln Likely pathogenic ★★ same condition
ARX p.Arg371Ter Pathogenic ★★ same condition
ARX p.Arg384Cys Pathogenic/Likely pathogenic ★★ same condition
ARX p.Glu294Ter Pathogenic ★★ 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-pro187 (accessed [today's date]).

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