Is ATRX p.Thr489= (c.1467C>T) pathogenic?

ATRX p.Thr489= (c.1467C>T) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-11). Ultra-rare (popmax 0.026%, nfe); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Thr489= (c.1467C>T)?

ATRX p.Thr489= (c.1467C>T) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Thr489= (c.1467C>T) in the general population?

ATRX p.Thr489= (c.1467C>T) is ultra-rare (popmax 0.026%, nfe) (gnomAD).

ATRX p.Thr489=

c.1467C>T · rs199929884 · VCV434462

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.026%, nfe)

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 0.65	GERP -5, phastCons 0.012
Overall
CADD	0.819	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.026% European (non-Finnish) · 232/893,081 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0221%

Overall 0.027% 326/1,207,535 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.204%	489
Remaining individualsnot grpmax-eligible	0.0316%	3,169
European (non-Finnish)grpmax	0.026%	3,849
South Asian	0.0247%	4,056
Middle Eastern	0.023%	4,350
Admixed American	0.0219%	4,573
East Asian	0.0148%	6,749
African / African-American	0.007%	14,295

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr489=
Coding: c.1467C>T
MANE Select: NM_000489
dbSNP: rs199929884
Type: single nucleotide variant
Location: chrX:77683789 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 489: 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.Thr489Ile 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-thr489 (accessed [today's date]).

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