Is ATRX p.Val936Phe (c.2806G>T) pathogenic?

ATRX p.Val936Phe (c.2806G>T) is classified Likely benign in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-09). AlphaMissense: likely benign (0.0876); Ultra-rare (popmax 0.0459%, mid); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Val936Phe (c.2806G>T)?

ATRX p.Val936Phe (c.2806G>T) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Val936Phe (c.2806G>T) in the general population?

ATRX p.Val936Phe (c.2806G>T) is ultra-rare (popmax 0.0459%, mid) (gnomAD).

What do computational predictors say about ATRX p.Val936Phe (c.2806G>T)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

ATRX p.Val936Phe

c.2806G>T · rs149232501 · VCV1158921

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0459%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -8.56	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 0.57	GERP 0.82, phastCons 0.96
Regional constraint	o/e 1.31	unconstrained · MANE · 2,828 bp · p 3.3e-15 · regional, not allelic
Overall
CADD	13.1	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 0.0459% Middle Eastern · 2/4,354 alleles

Filtering AF 0.00812% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0034%

Overall 0.000165% 2/1,211,303 alleles · ultra-rare exomes 2/1,097,944 · genomes 0/113,359 · joint denominator

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.Val936Phe
Coding: c.2806G>T
MANE Select: NM_000489
dbSNP: rs149232501
Type: single nucleotide variant
Location: chrX:77682450 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 936: 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 p.Val936Leu Conflicting classifications of pathogenicity ★ ⚠ 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
ATRX p.Arg2178Trp 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-val936phe (accessed [today's date]).

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