Is ATRX p.Arg37Ter (c.109C>T) pathogenic?

ATRX p.Arg37Ter (c.109C>T) is classified Pathogenic/Likely pathogenic in ATRX (ClinVar, Multiple submitters, 15 submitters; last evaluated 2025-08-15). Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATRX p.Arg37Ter (c.109C>T)?

ATRX p.Arg37Ter (c.109C>T) is associated with Inborn genetic diseases, intellectual disability, alpha-thalassemia-myelodysplastic syndrome (ClinVar).

How common is ATRX p.Arg37Ter (c.109C>T) in the general population?

ATRX p.Arg37Ter (c.109C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

ATRX p.Arg37Ter

c.109C>T · rs122445108 · VCV11742

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 35
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/892,216 alleles

Overall 9.14e-05% 1/1,094,244 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.Arg37Ter
Coding: c.109C>T
MANE Select: NM_000489
dbSNP: rs122445108
Type: single nucleotide variant
Location: chrX:77717155 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 37: the 'disordered' region

Full ATRX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability alpha-thalassemia-myelodysplastic syndrome alpha thalassemia-X-linked intellectual disability syndrome intellectual disability-hypotonic facies syndrome, X-linked, 1

Similar variants

ATRX p.Arg37Gln Uncertain significance ★ ⚠ same residue
ATRX p.Arg37Leu 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-arg37ter (accessed [today's date]).

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