Is ATRX p.Val921= (c.2763C>T) pathogenic?

ATRX p.Val921= (c.2763C>T) is classified Likely benign in ATRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-23). Very rare (popmax 0.00657%, amr); Associated with Inborn genetic diseases.

What condition is associated with ATRX p.Val921= (c.2763C>T)?

ATRX p.Val921= (c.2763C>T) is associated with Inborn genetic diseases, alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Val921= (c.2763C>T) in the general population?

ATRX p.Val921= (c.2763C>T) is very rare (popmax 0.00657%, amr) (gnomAD).

ATRX p.Val921=

c.2763C>T · rs782004945 · VCV533636

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00657%, amr)

Conditions

Inborn genetic diseases

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 -0.87	GERP -5.5
Overall
CADD	0.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00657% Admixed American · 3/45,684 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000883%

Overall 0.00141% 17/1,209,270 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00657%	15,228
East Asian	0.00296%	33,743
South Asian	0.00176%	56,786
European (non-Finnish)	0.00134%	74,578

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.Val921=
Coding: c.2763C>T
MANE Select: NM_000489
dbSNP: rs782004945
Type: single nucleotide variant
Location: chrX:77682493 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 921: 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: alpha thalassemia-X-linked intellectual disability syndrome

Similar variants

ATRX p.Val921Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
ATRX p.Val921Ile 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-val921 (accessed [today's date]).

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