Is ATRX p.Ile47Val (c.139A>G) pathogenic?

ATRX p.Ile47Val (c.139A>G) is classified Uncertain significance in ATRX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-17). AlphaMissense: likely benign (0.0647); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ATRX p.Ile47Val (c.139A>G)?

ATRX p.Ile47Val (c.139A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ATRX p.Ile47Val (c.139A>G) in the general population?

ATRX p.Ile47Val (c.139A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRX p.Ile47Val (c.139A>G)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

ATRX p.Ile47Val

c.139A>G · rs782584831 · VCV1691759

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	phastCons 0.032
Regional constraint	o/e 1.01	unconstrained · MANE · 89 kb · p 0.9 · regional, not allelic
Overall
CADD	11.22	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATRX
Protein: p.Ile47Val
Coding: c.139A>G
MANE Select: NM_000489
dbSNP: rs782584831
Type: single nucleotide variant
Location: chrX:77698624 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 47: 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

Similar variants

ATRX p.Ile47Thr Uncertain significance ★ ⚠ same residue
ATRX p.Arg246Cys Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Arg37Ter Pathogenic/Likely pathogenic ★★ same condition
ATRX p.Asn247Ser Likely pathogenic ★★ same condition
ATRX p.Cys220Tyr Pathogenic/Likely pathogenic ★★ same condition
ATRX c.4121-3A>G Uncertain significance ★★ same condition
ATRX c.6326+3A>G Uncertain significance ★★ same condition
ATRX p.Ala2356Val Uncertain significance ★★ ⚠ 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-ile47val (accessed [today's date]).

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