Is ATRX p.Ser384Arg (c.1150A>C) pathogenic?

ATRX p.Ser384Arg (c.1150A>C) is classified Likely benign in ATRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-14). AlphaMissense: likely benign (0.3339); Very rare (popmax 0.000336%, nfe); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Ser384Arg (c.1150A>C)?

ATRX p.Ser384Arg (c.1150A>C) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ser384Arg (c.1150A>C) in the general population?

ATRX p.Ser384Arg (c.1150A>C) is very rare (popmax 0.000336%, nfe) (gnomAD).

What do computational predictors say about ATRX p.Ser384Arg (c.1150A>C)?

AlphaMissense predicts likely benign (score 0.3339) — an in-silico prediction, not a clinical call.

ATRX p.Ser384Arg

c.1150A>C · rs782196033 · VCV1289393

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000336%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

Computational evidence

Protein change
AlphaMissense	0.3339	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.044, phastCons 0.86
Regional constraint	o/e 1.31	unconstrained · MANE · 2,828 bp · p 3.3e-15 · regional, not allelic
Overall
CADD	17.33	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000336% European (non-Finnish) · 3/892,896 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000274% 3/1,094,411 alleles · very rare

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.Ser384Arg
Coding: c.1150A>C
MANE Select: NM_000489
dbSNP: rs782196033
Type: single nucleotide variant
Location: chrX:77684106 (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 p.Ser384Gly Uncertain significance ★★ ⚠ same residue
ATRX p.Ser384Thr 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

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-ser384arg (accessed [today's date]).

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