Is DDX3X p.Ser58Ter (c.173C>G) pathogenic?

DDX3X p.Ser58Ter (c.173C>G) is classified Pathogenic/Likely pathogenic in DDX3X (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-02). Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 102.

What condition is associated with DDX3X p.Ser58Ter (c.173C>G)?

DDX3X p.Ser58Ter (c.173C>G) is associated with intellectual disability, X-linked 102 (ClinVar).

How common is DDX3X p.Ser58Ter (c.173C>G) in the general population?

DDX3X p.Ser58Ter (c.173C>G) is absent from gnomAD v4.1 (gnomAD).

DDX3X p.Ser58Ter

c.173C>G · rs1602126980 · VCV803981

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual disability, X-linked 102

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

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.Ser58Ter
Coding: c.173C>G
MANE Select: NM_001356
dbSNP: rs1602126980
Type: single nucleotide variant
Location: chrX:41341505 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 58: the 'required for tbk1 and ikbke-dependent ifnb1 activation' region; the 'disordered' 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.Ser58Ala 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-ser58ter (accessed [today's date]).

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