Is ATRX p.Asp699fs (c.2093dup) pathogenic?

ATRX p.Asp699fs (c.2093dup) is classified Likely pathogenic in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-16). Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Asp699fs (c.2093dup)?

ATRX p.Asp699fs (c.2093dup) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

ATRX p.Asp699fs

c.2093dup · VCV4818456

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

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 0.51	GERP -5.9, phastCons 1

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

Variant & gene context

Gene: ATRX
Protein: p.Asp699fs
Coding: c.2093dup
MANE Select: NM_000489
Type: Duplication
Location: chrX:77683162 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 699: the 'disordered' region

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

Disease context

alpha thalassemia-X-linked intellectual disability syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATRX c.243-8dup Likely benign ★★ same condition
ATRX p.Ser645fs Pathogenic ★ same condition
ATRX p.Thr1582fs Likely pathogenic ★ same condition
ATRX p.Thr894fs Pathogenic ★ same condition
ATRX p.Asp699His Uncertain significance ★ ⚠ same residue
ATRX p.Glu1460_Glu1464dup Uncertain significance ★ same condition
ATRX c.21-6dup Benign ★ same condition
ATRX c.3737-9dup Benign ★ 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-asp699fs (accessed [today's date]).

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