Is DDX3X p.Arg99= (c.297T>C) pathogenic?

DDX3X p.Arg99= (c.297T>C) is classified Likely benign in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-23). Absent from gnomAD v4.1.

How common is DDX3X p.Arg99= (c.297T>C) in the general population?

DDX3X p.Arg99= (c.297T>C) is absent from gnomAD v4.1 (gnomAD).

DDX3X p.Arg99=

c.297T>C · rs2519508517 · VCV2861869

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP 1.1, phastCons 1
Overall
CADD	10.32	PHRED · no single calibrated threshold — expert panels disagree

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.Arg99=
Coding: c.297T>C
MANE Select: NM_001356
dbSNP: rs2519508517
Type: single nucleotide variant
Location: chrX:41342507 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 99: the 'required for tbk1 and ikbke-dependent ifnb1 activation' region; the 'disordered' region; the 'involved in binding to rna g-quadruplex' region

Full DDX3X gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX3X p.Arg99Cys Uncertain significance ★ ⚠ same residue
DDX3X c.1497+1G>A Likely pathogenic ★★ same type
DDX3X c.1498-2A>G Pathogenic ★★ same type
DDX3X c.151+1G>A Pathogenic ★★ same type
DDX3X c.1769+1G>A Pathogenic ★★ same type
DDX3X c.765+1G>A Pathogenic ★★ same type
DDX3X c.865-1G>A Pathogenic ★★ same type
DDX3X c.865-1G>C Pathogenic ★★ same type

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-arg99 (accessed [today's date]).

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