Is ATRX p.Ile1035Val (c.3103A>G) pathogenic?

ATRX p.Ile1035Val (c.3103A>G) is classified Benign/Likely benign in ATRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.0738); Very rare (popmax 0.00123%, nfe); Associated with alpha thalassemia-X-linked intellectual disability syndrome.

What condition is associated with ATRX p.Ile1035Val (c.3103A>G)?

ATRX p.Ile1035Val (c.3103A>G) is associated with alpha thalassemia-X-linked intellectual disability syndrome (ClinVar).

How common is ATRX p.Ile1035Val (c.3103A>G) in the general population?

ATRX p.Ile1035Val (c.3103A>G) is very rare (popmax 0.00123%, nfe) (gnomAD).

What do computational predictors say about ATRX p.Ile1035Val (c.3103A>G)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

ATRX p.Ile1035Val

c.3103A>G · rs781916347 · VCV1600206

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00123%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

alpha thalassemia-X-linked intellectual disability syndrome

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.89	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 1.4	GERP 1.3, phastCons 0.93
Regional constraint	o/e 1.31	unconstrained · MANE · 2,828 bp · p 3.3e-15 · regional, not allelic
Overall
CADD	15.3	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 0.00123% European (non-Finnish) · 11/894,966 alleles

Filtering AF 0.000659% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000482%

Overall 0.000909% 11/1,209,681 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.Ile1035Val
Coding: c.3103A>G
MANE Select: NM_000489
dbSNP: rs781916347
Type: single nucleotide variant
Location: chrX:77682153 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 1035: 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.Ile1035= Benign ★ 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-ile1035val (accessed [today's date]).

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