Is ATRX p.Gln545Glu (c.1633C>G) pathogenic?

ATRX p.Gln545Glu (c.1633C>G) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0729); Low-frequency (popmax 2.2%, afr); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Gln545Glu (c.1633C>G)?

ATRX p.Gln545Glu (c.1633C>G) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Gln545Glu (c.1633C>G) in the general population?

ATRX p.Gln545Glu (c.1633C>G) is low-frequency (popmax 2.2%, afr) (gnomAD).

What do computational predictors say about ATRX p.Gln545Glu (c.1633C>G)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

ATRX p.Gln545Glu

c.1633C>G · rs35738915 · VCV93132

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.2%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -4.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.31	unconstrained · MANE · 2,828 bp · p 3.3e-15 · regional, not allelic
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.2% African / African-American · 1,260/57,221 alleles

Filtering AF 2.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.06%

Overall 0.115% 1,391/1,209,806 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.2%	45
Admixed American	0.142%	704
Remaining individualsnot grpmax-eligible	0.107%	934
Middle Eastern	0.0459%	2,177
South Asian	0.00528%	18,935
European (non-Finnish)	0.00112%	89,501

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.Gln545Glu
Coding: c.1633C>G
MANE Select: NM_000489
dbSNP: rs35738915
Type: single nucleotide variant
Location: chrX:77683623 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 545: a UniProt-annotated variant site (in); 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-gln545glu (accessed [today's date]).

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