Is DDX4 p.Arg577Ser (c.1731A>C) pathogenic?

DDX4 p.Arg577Ser (c.1731A>C) is classified Uncertain significance in DDX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). AlphaMissense: likely pathogenic (0.7791); Absent from gnomAD v4.1.

How common is DDX4 p.Arg577Ser (c.1731A>C) in the general population?

DDX4 p.Arg577Ser (c.1731A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX4 p.Arg577Ser (c.1731A>C)?

AlphaMissense predicts likely pathogenic (score 0.7791) — an in-silico prediction, not a clinical call.

DDX4 p.Arg577Ser

c.1731A>C · VCV4659079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7791 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7791	likely pathogenic
REVEL	0.347	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -0.58, phastCons 0.95
Regional constraint	o/e 0.51	unconstrained · MANE · 22 kb · p 2.5e-13 · regional, not allelic
Overall
CADD	23.0	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.Arg577Ser
Coding: c.1731A>C
MANE Select: NM_024415
Type: single nucleotide variant
Location: chr5:55814916 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.06
Residue 577: the helicase c-terminal domain

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-arg577ser (accessed [today's date]).

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