Is ATRX p.Ser1396= (c.4188C>T) pathogenic?

ATRX p.Ser1396= (c.4188C>T) is classified Benign in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-18). Very rare (popmax 0.00297%, eas); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Ser1396= (c.4188C>T)?

ATRX p.Ser1396= (c.4188C>T) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ser1396= (c.4188C>T) in the general population?

ATRX p.Ser1396= (c.4188C>T) is very rare (popmax 0.00297%, eas) (gnomAD).

ATRX p.Ser1396=

c.4188C>T · rs966422483 · VCV2986077

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00297%, eas)

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 0.45	GERP -5, phastCons 0.55
Overall
CADD	3.949	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% East Asian · 1/33,702 alleles

Filtering AF 0.000385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000822% 9/1,094,469 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00297%	33,702
European (non-Finnish)	0.000896%	111,660

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.Ser1396=
Coding: c.4188C>T
MANE Select: NM_000489
dbSNP: rs966422483
Type: single nucleotide variant
Location: chrX:77656586 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 1396: 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-ser1396 (accessed [today's date]).

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