Is DDX41 p.Phe478fs (c.1431del) pathogenic?

DDX41 p.Phe478fs (c.1431del) is classified Pathogenic/Likely pathogenic in DDX41 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-09). Absent from gnomAD; Associated with DDX41-related disorders.

What condition is associated with DDX41 p.Phe478fs (c.1431del)?

DDX41 p.Phe478fs (c.1431del) is associated with DDX41-related disorders (ClinVar).

How common is DDX41 p.Phe478fs (c.1431del) in the general population?

DDX41 p.Phe478fs (c.1431del) is absent from gnomAD (gnomAD).

DDX41 p.Phe478fs

c.1431del · rs2532075844 · VCV2111172

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

DDX41-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DDX41
Protein: p.Phe478fs
Coding: c.1431del
MANE Select: NM_016222
dbSNP: rs2532075844
Type: Deletion
Location: chr5:177512614 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 478: the helicase c-terminal domain; an α-helix

Full DDX41 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DDX41-related disorders

Similar variants

DDX41 c.138+2_138+19del Likely pathogenic ★ same condition
DDX41 p.Ile142fs Likely pathogenic ★ same condition
DDX41 c.434+1G>A Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Ala500fs Pathogenic ★★ same condition
DDX41 p.Asp140delinsGlyTer Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Gln272Ter Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Gln41Ter Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Gln48Ter Pathogenic/Likely pathogenic ★★ same condition

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/ddx41-p-phe478fs (accessed [today's date]).

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