Is ATRX p.Lys1114= (c.3342A>G) pathogenic?

ATRX p.Lys1114= (c.3342A>G) is classified Benign in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). Very rare (popmax 0.00351%, sas); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Lys1114= (c.3342A>G)?

ATRX p.Lys1114= (c.3342A>G) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Lys1114= (c.3342A>G) in the general population?

ATRX p.Lys1114= (c.3342A>G) is very rare (popmax 0.00351%, sas) (gnomAD).

ATRX p.Lys1114=

c.3342A>G · VCV3667335

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00351%, 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 0.35, phastCons 1
Overall
CADD	7.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00351% South Asian · 2/56,936 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000273% 3/1,097,560 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00351%	28,468
Remaining individualsnot grpmax-eligible	0.0021%	47,619

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.Lys1114=
Coding: c.3342A>G
MANE Select: NM_000489
Type: single nucleotide variant
Location: chrX:77681914 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 1114: 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-lys1114 (accessed [today's date]).

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