Is ATRX p.Asp217Val (c.650A>T) pathogenic?

ATRX p.Asp217Val (c.650A>T) is classified Uncertain significance in ATRX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-13). AlphaMissense: likely pathogenic (0.9924); Absent from gnomAD v4.1.

How common is ATRX p.Asp217Val (c.650A>T) in the general population?

ATRX p.Asp217Val (c.650A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRX p.Asp217Val (c.650A>T)?

AlphaMissense predicts likely pathogenic (score 0.9924) — an in-silico prediction, not a clinical call.

ATRX p.Asp217Val

c.650A>T · VCV3769720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9924 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9924	likely pathogenic
REVEL	0.867	moderately pathogenic-leaning
SaProt	LLR -11.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 2.6, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 4,427 bp · p 3.6e-13 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Asp217Val
Coding: c.650A>T
MANE Select: NM_000489
Type: single nucleotide variant
Location: chrX:77684951 (GRCh38)
Structure: AlphaFold pLDDT 52.40 · 13 PDB
Residue 217: the add domain; a β-strand

Full ATRX gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATRX p.Asp217Asn Uncertain significance ★ ⚠ same residue
ATRX c.134-2A>G Pathogenic/Likely pathogenic ★★ same type
ATRX c.5449-7A>G Likely pathogenic ★★ same type
ATRX p.Arg1022Ter Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg1661Cys Likely pathogenic ★★ ⚠ same type
ATRX p.Arg2085Cys Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg2085His Pathogenic/Likely pathogenic ★★ same type
ATRX p.Arg2131Gln Pathogenic/Likely pathogenic ★★ same type

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-asp217val (accessed [today's date]).

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