Is ATRX p.Ser344= (c.1032C>T) pathogenic?

ATRX p.Ser344= (c.1032C>T) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0105%, afr); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Ser344= (c.1032C>T)?

ATRX p.Ser344= (c.1032C>T) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ser344= (c.1032C>T) in the general population?

ATRX p.Ser344= (c.1032C>T) is ultra-rare (popmax 0.0105%, afr) (gnomAD).

ATRX p.Ser344=

c.1032C>T · rs143491422 · VCV699729

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, afr)

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 0.46	GERP -2.3, phastCons 0.99
Overall
CADD	2.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% African / African-American · 6/57,264 alleles

Filtering AF 0.00456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00546% 66/1,209,287 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0105%	9,544
East Asian	0.00592%	16,885
European (non-Finnish)	0.00559%	17,898
South Asian	0.00529%	18,912
Admixed American	0.00437%	22,867
Remaining individualsnot grpmax-eligible	0.0042%	23,796
Finnishnot grpmax-eligible	0.00216%	46,238

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.Ser344=
Coding: c.1032C>T
MANE Select: NM_000489
dbSNP: rs143491422
Type: single nucleotide variant
Location: chrX:77684224 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB

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-ser344 (accessed [today's date]).

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