Is ATRX p.Lys96= (c.288A>G) pathogenic?

ATRX p.Lys96= (c.288A>G) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 16.5%, amr) — too common for a highly-penetrant pathogenic allele; Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Lys96= (c.288A>G)?

ATRX p.Lys96= (c.288A>G) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

ATRX p.Lys96=

Q: How common is ATRX p.Lys96= (c.288A>G) in the general population?

ATRX p.Lys96= (c.288A>G) is common (popmax 16.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.288A>G · rs45574238 · VCV93136

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 16.5%, amr) — too common for a highly-penetrant pathogenic allele

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 3.3	phastCons 1
Overall
CADD	9.236	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.5% Admixed American · 7,523/45,553 alleles

Filtering AF 16.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.1%

Overall 0.772% 9,233/1,196,425 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	16.5%	6
Remaining individualsnot grpmax-eligible	0.907%	110
African / African-American	0.212%	471
South Asian	0.143%	701
European (non-Finnish)	0.121%	823
Middle Eastern	0.0468%	2,139
East Asian	0.00891%	11,224
Ashkenazi Jewishnot grpmax-eligible	0.00457%	21,900
Finnishnot grpmax-eligible	0.0043%	23,260

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.Lys96=
Coding: c.288A>G
MANE Select: NM_000489
dbSNP: rs45574238
Type: single nucleotide variant
Location: chrX:77696659 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 96: 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.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
ATRX p.Arg2386Ter 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-lys96 (accessed [today's date]).

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