Is ATRX p.Arg444Ter (c.1330C>T) pathogenic?

ATRX p.Arg444Ter (c.1330C>T) is classified Likely pathogenic in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-03). Very rare (popmax 0.000224%, nfe).

How common is ATRX p.Arg444Ter (c.1330C>T) in the general population?

ATRX p.Arg444Ter (c.1330C>T) is very rare (popmax 0.000224%, nfe) (gnomAD).

ATRX p.Arg444Ter

c.1330C>T · rs2148625435 · VCV2436330

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000224%, nfe)

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 9 of 35
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.8, phastCons 0.57
Overall
CADD	24.1	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 0.000224% European (non-Finnish) · 2/894,010 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000182% 2/1,096,228 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.Arg444Ter
Coding: c.1330C>T
MANE Select: NM_000489
dbSNP: rs2148625435
Type: single nucleotide variant
Location: chrX:77683926 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB

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

Similar variants

ATRX p.Arg444= Likely benign ★★ same residue
ATRX p.Arg444Gln Likely benign ★ same residue
ATRX c.134-2A>G Pathogenic/Likely pathogenic ★★ same type
ATRX c.5449-7A>G Likely pathogenic ★★ same type
ATRX p.Arg1022Ter Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg1661Cys Likely pathogenic ★★ ⚠ same type
ATRX p.Arg2085Cys Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same type

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-arg444ter (accessed [today's date]).

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