Is DDX3X p.Ser90fs (c.269dup) pathogenic?

DDX3X p.Ser90fs (c.269dup) is classified Pathogenic in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Absent from gnomAD; Associated with intellectual disability, X-linked 102.

What condition is associated with DDX3X p.Ser90fs (c.269dup)?

DDX3X p.Ser90fs (c.269dup) is associated with intellectual disability, X-linked 102 (ClinVar).

How common is DDX3X p.Ser90fs (c.269dup) in the general population?

DDX3X p.Ser90fs (c.269dup) is absent from gnomAD (gnomAD).

DDX3X p.Ser90fs

c.269dup · rs1602127262 · VCV803982

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability, X-linked 102

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.9	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DDX3X
Protein: p.Ser90fs
Coding: c.269dup
MANE Select: NM_001356
dbSNP: rs1602127262
Type: Duplication
Location: chrX:41341600 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 90: a modified residue (phosphoserine); the 'required for tbk1 and ikbke-dependent ifnb1 activation' region; the 'disordered' region; the 'interaction with vacv protein k7' region; the 'involved in binding to rna g-quadruplex' 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.Asn546Ter Pathogenic ★★ same condition
DDX3X c.1171-8dup Benign/Likely benign ★★ same condition
DDX3X p.Ala501fs Pathogenic ★ same condition
DDX3X p.Arg101fs Pathogenic ★ same condition
DDX3X p.Arg311fs Pathogenic ★ same condition
DDX3X p.Arg394_Asp395dup Likely pathogenic ★ same condition
DDX3X p.Asn414fs Likely pathogenic ★ same condition
DDX3X p.Asp77fs 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-ser90fs (accessed [today's date]).

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