Is DDX4 p.Arg63Gln (c.188G>A) pathogenic?

DDX4 p.Arg63Gln (c.188G>A) is classified Uncertain significance in DDX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1051); Ultra-rare (popmax 0.0604%, sas).

How common is DDX4 p.Arg63Gln (c.188G>A) in the general population?

DDX4 p.Arg63Gln (c.188G>A) is ultra-rare (popmax 0.0604%, sas) (gnomAD).

What do computational predictors say about DDX4 p.Arg63Gln (c.188G>A)?

AlphaMissense predicts likely benign (score 0.1051) — an in-silico prediction, not a clinical call.

DDX4 p.Arg63Gln

c.188G>A · VCV4238696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1051 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0604%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1051	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 54 kb · p 4.6e-05 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0604% South Asian · 50/82,838 alleles

Filtering AF 0.047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.00453% 71/1,568,654 alleles · ultra-rare exomes 68/1,416,550 · genomes 3/152,104 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0604%	1,657
Middle Eastern	0.0168%	5,968
European (non-Finnish)	0.00172%	58,176

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: DDX4
Protein: p.Arg63Gln
Coding: c.188G>A
MANE Select: NM_024415
Type: single nucleotide variant
Location: chr5:55760260 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.06
Residue 63: the 'disordered' region

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

Similar variants

DDX4 p.Arg63Gly Uncertain significance ★ ⚠ same residue
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

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-arg63gln (accessed [today's date]).

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