Is ATRX p.Ser1204= (c.3612T>A) pathogenic?

ATRX p.Ser1204= (c.3612T>A) is classified Benign in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-10). Very rare (popmax 0.0036%, sas); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Ser1204= (c.3612T>A)?

ATRX p.Ser1204= (c.3612T>A) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ser1204= (c.3612T>A) in the general population?

ATRX p.Ser1204= (c.3612T>A) is very rare (popmax 0.0036%, sas) (gnomAD).

ATRX p.Ser1204=

c.3612T>A · rs781968655 · VCV2897556

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0036%, sas)

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 -1.4	GERP -4.6, phastCons 0.014
Overall
CADD	0.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0036% South Asian · 2/55,573 alleles

Filtering AF 0.000597% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000223%

Overall 0.000249% 3/1,205,988 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0036%	27,786
African / African-American	0.00175%	57,026

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.Ser1204=
Coding: c.3612T>A
MANE Select: NM_000489
dbSNP: rs781968655
Type: single nucleotide variant
Location: chrX:77681644 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 1204: the 'disordered' region; the 'interaction with daxx' 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.Ser1204Cys 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-ser1204 (accessed [today's date]).

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