Is ATRX p.Cys243Arg (c.727T>C) pathogenic?

ATRX p.Cys243Arg (c.727T>C) is classified Likely pathogenic in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Cys243Arg (c.727T>C)?

ATRX p.Cys243Arg (c.727T>C) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Cys243Arg (c.727T>C) in the general population?

ATRX p.Cys243Arg (c.727T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRX p.Cys243Arg (c.727T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

ATRX p.Cys243Arg

c.727T>C · VCV4063628

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 3% in ATRX
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -14.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 4,427 bp · p 3.6e-13 · regional, not allelic
Overall
CADD	24.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATRX
Protein: p.Cys243Arg
Coding: c.727T>C
MANE Select: NM_000489
Type: single nucleotide variant
Location: chrX:77684529 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 243: the add domain; a UniProt-annotated variant site (in atrx); an α-helix

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.Cys243Trp Likely pathogenic ★★ same residue
ATRX p.Cys243Tyr Likely pathogenic ★ 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-cys243arg (accessed [today's date]).

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