Is ATRX p.Glu990= (c.2970A>G) pathogenic?

ATRX p.Glu990= (c.2970A>G) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Rare (popmax 0.159%, sas); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Glu990= (c.2970A>G)?

ATRX p.Glu990= (c.2970A>G) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Glu990= (c.2970A>G) in the general population?

ATRX p.Glu990= (c.2970A>G) is rare (popmax 0.159%, sas) (gnomAD).

ATRX p.Glu990=

c.2970A>G · rs782253066 · VCV589073

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.159%, sas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.048	GERP -5.2, phastCons 0.003
Overall
CADD	0.563	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.159% South Asian · 85/53,450 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.00735% 88/1,198,041 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.159%	629
East Asian	0.00297%	33,713
Remaining individualsnot grpmax-eligible	0.00212%	47,064
European (non-Finnish)	0.000112%	891,870

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: ATRX
Protein: p.Glu990=
Coding: c.2970A>G
MANE Select: NM_000489
dbSNP: rs782253066
Type: single nucleotide variant
Location: chrX:77682286 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 990: 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 p.Glu990Lys Likely benign ★★ same residue
ATRX c.5449-7A>G Likely pathogenic ★★ same condition
ATRX p.Arg1022Ter Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg1661Cys Likely pathogenic ★★ ⚠ same condition
ATRX p.Arg2085Cys Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg2131Gln Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg2178Trp Pathogenic/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-glu990 (accessed [today's date]).

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