Is DDX3X p.Pro40Ser (c.118C>T) pathogenic?

DDX3X p.Pro40Ser (c.118C>T) is classified Likely pathogenic in DDX3X (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-28). AlphaMissense: likely pathogenic (0.996); Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 102.

What condition is associated with DDX3X p.Pro40Ser (c.118C>T)?

DDX3X p.Pro40Ser (c.118C>T) is associated with intellectual disability, X-linked 102 (ClinVar).

How common is DDX3X p.Pro40Ser (c.118C>T) in the general population?

DDX3X p.Pro40Ser (c.118C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX3X p.Pro40Ser (c.118C>T)?

AlphaMissense predicts likely pathogenic (score 0.996) — an in-silico prediction, not a clinical call.

DDX3X p.Pro40Ser

c.118C>T · rs1602122138 · VCV810576

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability, X-linked 102

Computational evidence

Protein change
AlphaMissense	0.996	likely pathogenic ✓ concordant with ClinVar
REVEL	0.352	indeterminate
SaProt	LLR -8.31	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,391 bp · p 0.0057 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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.Pro40Ser
Coding: c.118C>T
MANE Select: NM_001356
dbSNP: rs1602122138
Type: single nucleotide variant
Location: chrX:41339050 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 40: the 'required for tbk1 and ikbke-dependent ifnb1 activation' region; the 'disordered' region; the 'interaction with eif4e' 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.Pro40Leu Conflicting classifications of pathogenicity ★ same residue
DDX3X p.Pro40Arg 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
DDX3X p.Arg292Ter 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-pro40ser (accessed [today's date]).

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