Is DDX4 p.Arg698Ile (c.2093G>T) pathogenic?

DDX4 p.Arg698Ile (c.2093G>T) is classified Uncertain significance in DDX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely pathogenic (0.9562); Absent from gnomAD v4.1.

How common is DDX4 p.Arg698Ile (c.2093G>T) in the general population?

DDX4 p.Arg698Ile (c.2093G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX4 p.Arg698Ile (c.2093G>T)?

AlphaMissense predicts likely pathogenic (score 0.9562) — an in-silico prediction, not a clinical call.

DDX4 p.Arg698Ile

c.2093G>T · VCV4010238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9562 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9562	likely pathogenic
REVEL	0.339	indeterminate
SaProt	LLR -9.43	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 1,435 bp · p 0.01 · regional, not allelic
Overall
CADD	28.0	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: DDX4
Protein: p.Arg698Ile
Coding: c.2093G>T
MANE Select: NM_024415
Type: single nucleotide variant
Location: chr5:55815419 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.06

Full DDX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX4 c.1172+9A>G Benign ★★ same type
DDX4 p.Ala448= Benign ★★ same type
DDX4 p.Lys472Glu Benign ★★ same type
DDX4 p.Ala304Val Uncertain significance ★ ⚠ same type
DDX4 p.Ala385Val Uncertain significance ★ ⚠ same type
DDX4 p.Ala493Val Uncertain significance ★ ⚠ same type
DDX4 p.Ala511Val Uncertain significance ★ same type
DDX4 p.Arg111Lys Uncertain significance ★ ⚠ 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/ddx4-p-arg698ile (accessed [today's date]).

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