Is ATRX p.Pro592fs (c.1775_1776del) pathogenic?

ATRX p.Pro592fs (c.17751776del) is classified Likely pathogenic in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). Associated with ATRX-related disorder.

What condition is associated with ATRX p.Pro592fs (c.1775_1776del)?

ATRX p.Pro592fs (c.1775_1776del) is associated with ATRX-related disorder (ClinVar).

ATRX p.Pro592fs

c.1775_1776del · VCV4951688

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ATRX-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 9 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ATRX
Protein: p.Pro592fs
Coding: c.1775_1776del
MANE Select: NM_000489
Type: Deletion
Location: chrX:77683480 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB

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

Disease context

ATRX-related disorder

Similar variants

ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg2131Gln Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Phe1780Tyr Likely pathogenic ★★ same condition
ATRX p.Cys280Arg Uncertain significance ★★ ⚠ same condition
ATRX p.Ser1067Leu Uncertain significance ★★ ⚠ same condition
ATRX p.Thr2117Ala Uncertain significance ★★ ⚠ same condition
ATRX p.Asn156fs Pathogenic ★ same condition
ATRX p.Asp1615Glu Likely 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/atrx-p-pro592fs (accessed [today's date]).

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