Is ATRX p.Gln182= (c.546A>G) pathogenic?

ATRX p.Gln182= (c.546A>G) is classified Likely benign in ATRX (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-30). Ultra-rare (popmax 0.0349%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATRX p.Gln182= (c.546A>G)?

ATRX p.Gln182= (c.546A>G) is associated with Inborn genetic diseases, alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Gln182= (c.546A>G) in the general population?

ATRX p.Gln182= (c.546A>G) is ultra-rare (popmax 0.0349%, afr) (gnomAD).

ATRX p.Gln182=

c.546A>G · rs375794120 · VCV465062

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0349%, afr)

Conditions

Inborn genetic diseases

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 -0.3	GERP -4.8, phastCons 0.42
Overall
CADD	5.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0349% African / African-American · 20/57,331 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0193%

Overall 0.00198% 24/1,209,739 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0349%	2,867
Admixed American	0.00219%	45,766
European (non-Finnish)	0.000335%	298,327

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.Gln182=
Coding: c.546A>G
MANE Select: NM_000489
dbSNP: rs375794120
Type: single nucleotide variant
Location: chrX:77688866 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 182: the add domain; a UniProt-annotated variant site (in atrx)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: alpha thalassemia-X-linked intellectual disability syndrome

Similar variants

ATRX p.Gln182His Uncertain significance ★ ⚠ 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-gln182 (accessed [today's date]).

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