Is DDX3X p.Arg603= (c.1809A>G) pathogenic?

DDX3X p.Arg603= (c.1809A>G) is classified Likely benign in DDX3X (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-15). Very rare (popmax 0.00217%, amr).

How common is DDX3X p.Arg603= (c.1809A>G) in the general population?

DDX3X p.Arg603= (c.1809A>G) is very rare (popmax 0.00217%, amr) (gnomAD).

DDX3X p.Arg603=

c.1809A>G · rs2063939994 · VCV1965619

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

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 -0.088	GERP -4.8, phastCons 0.005
Overall
CADD	5.373	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00217% Admixed American · 1/46,034 alleles

Overall 9.11e-05% 1/1,097,826 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DDX3X
Protein: p.Arg603=
Coding: c.1809A>G
MANE Select: NM_001356
dbSNP: rs2063939994
Type: single nucleotide variant
Location: chrX:41347351 (GRCh38)
Structure: AlphaFold pLDDT 73.24 · 17 PDB
Residue 603: the 'interaction with hcv core protein' region; the 'interaction with nxf1' region; the 'disordered' region; the 'interaction with gsk3b' region

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

Similar variants

DDX3X p.Arg603Ter Pathogenic ★★ same residue
DDX3X p.Arg603Gln Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg603 (accessed [today's date]).

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