Is DDX3X p.Arg480fs (c.1439_1440insTCTC) pathogenic?

DDX3X p.Arg480fs (c.14391440insTCTC) is classified Pathogenic in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-29). Absent from gnomAD; Associated with intellectual disability, X-linked 102.

What condition is associated with DDX3X p.Arg480fs (c.1439_1440insTCTC)?

DDX3X p.Arg480fs (c.1439_1440insTCTC) is associated with intellectual disability, X-linked 102 (ClinVar).

How common is DDX3X p.Arg480fs (c.1439_1440insTCTC) in the general population?

DDX3X p.Arg480fs (c.1439_1440insTCTC) is absent from gnomAD (gnomAD).

DDX3X p.Arg480fs

c.1439_1440insTCTC · rs2519523296 · VCV1802581

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 13 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.4, 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.Arg480fs
Coding: c.1439_1440insTCTC
MANE Select: NM_001356
dbSNP: rs2519523296
Type: Insertion
Location: chrX:41346352 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 480: the 'interaction with hcv core protein' region; an α-helix; the helicase c-terminal domain; a UniProt-annotated variant site (in mrxssb); 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.Arg480Gly Pathogenic/Likely pathogenic ★★ same residue
DDX3X p.Arg480Thr Pathogenic ★ same residue
DDX3X p.Arg480_Glu481delinsLys Pathogenic ★ 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

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-arg480fs (accessed [today's date]).

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