Is ATRX p.Thr894Pro (c.2680A>C) pathogenic?

ATRX p.Thr894Pro (c.2680A>C) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0933); Ultra-rare (popmax 0.0873%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATRX p.Thr894Pro (c.2680A>C)?

ATRX p.Thr894Pro (c.2680A>C) is associated with Inborn genetic diseases, alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Thr894Pro (c.2680A>C) in the general population?

ATRX p.Thr894Pro (c.2680A>C) is ultra-rare (popmax 0.0873%, afr) (gnomAD).

What do computational predictors say about ATRX p.Thr894Pro (c.2680A>C)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

ATRX p.Thr894Pro

c.2680A>C · rs145807475 · VCV133650

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0873%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.022	GERP -0.008, phastCons 0.13
Regional constraint	o/e 1.31	unconstrained · MANE · 2,828 bp · p 3.3e-15 · regional, not allelic
Overall
CADD	12.31	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

Grpmax group 0.0873% African / African-American · 50/57,262 alleles

Filtering AF 0.068% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0611%

Overall 0.00471% 57/1,209,135 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0873%	1,145
Admixed American	0.00875%	11,431
Remaining individualsnot grpmax-eligible	0.0042%	23,798
European (non-Finnish)	0.000112%	894,783

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.Thr894Pro
Coding: c.2680A>C
MANE Select: NM_000489
dbSNP: rs145807475
Type: single nucleotide variant
Location: chrX:77682576 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 894: 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.Thr894Ile Benign ★ same residue
ATRX p.Thr894fs 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-thr894pro (accessed [today's date]).

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