Is DDX3X p.Ser293Phe (c.878C>T) pathogenic?

DDX3X p.Ser293Phe (c.878C>T) is classified Likely pathogenic in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). AlphaMissense: likely pathogenic (0.999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DDX3X p.Ser293Phe (c.878C>T)?

DDX3X p.Ser293Phe (c.878C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DDX3X p.Ser293Phe (c.878C>T) in the general population?

DDX3X p.Ser293Phe (c.878C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX3X p.Ser293Phe (c.878C>T)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

DDX3X p.Ser293Phe

c.878C>T · rs2519515024 · VCV2545947

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic ✓ concordant with ClinVar
REVEL	0.467	indeterminate
SaProt	LLR -16.07	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 1.5, phastCons 1
Regional constraint	o/e 0.24	constrained · MANE · 3,927 bp · p 1.5e-39 · regional, not allelic
Overall
CADD	31.0	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.Ser293Phe
Coding: c.878C>T
MANE Select: NM_001356
dbSNP: rs2519515024
Type: single nucleotide variant
Location: chrX:41344252 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 293: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDX3X c.1498-2A>G Pathogenic ★★ same condition
DDX3X c.151+1G>A Pathogenic ★★ same condition
DDX3X c.1769+1G>A Pathogenic ★★ same condition
DDX3X c.865-1G>C Pathogenic ★★ same condition
DDX3X p.Ala497Val Pathogenic/Likely pathogenic ★★ same condition
DDX3X p.Arg292Ter Pathogenic/Likely pathogenic ★★ same condition
DDX3X p.Arg326Cys Pathogenic/Likely pathogenic ★★ same condition
DDX3X p.Arg376Cys 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-ser293phe (accessed [today's date]).

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