Is DDX3X p.Ala286Asp (c.857C>A) pathogenic?

DDX3X p.Ala286Asp (c.857C>A) is classified Uncertain significance in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-11). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 102.

What condition is associated with DDX3X p.Ala286Asp (c.857C>A)?

DDX3X p.Ala286Asp (c.857C>A) is associated with intellectual disability, X-linked 102 (ClinVar).

How common is DDX3X p.Ala286Asp (c.857C>A) in the general population?

DDX3X p.Ala286Asp (c.857C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX3X p.Ala286Asp (c.857C>A)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

DDX3X p.Ala286Asp

c.857C>A · rs2063889955 · VCV932105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, X-linked 102

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 8% in DDX3X
REVEL	0.598	indeterminate
SaProt	LLR -12.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 3,927 bp · p 1.5e-39 · regional, not allelic
Overall
CADD	29.2	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: DDX3X
Protein: p.Ala286Asp
Coding: c.857C>A
MANE Select: NM_001356
dbSNP: rs2063889955
Type: single nucleotide variant
Location: chrX:41344121 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 286: an α-helix; the helicase atp-binding domain; the 'interaction with gsk3b' region

Full DDX3X gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 102 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDX3X p.Ala286Pro Uncertain significance ★ ⚠ same residue
DDX3X c.1497+1G>A Likely pathogenic ★★ same condition
DDX3X c.865-1G>A Pathogenic ★★ same condition
DDX3X c.865-2A>G Pathogenic ★★ same condition
DDX3X p.Ala349Thr Pathogenic/Likely pathogenic ★★ same condition
DDX3X p.Ala497Val Pathogenic/Likely pathogenic ★★ same condition
DDX3X p.Arg292Ter Pathogenic/Likely pathogenic ★★ same condition
DDX3X p.Arg311Ter 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/ddx3x-p-ala286asp (accessed [today's date]).

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