Is DDX41 p.Phe535fs (c.1603_1605delinsA) pathogenic?

DDX41 p.Phe535fs (c.16031605delinsA) is classified Pathogenic in DDX41 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-05). Absent from gnomAD; Associated with DDX41-related hematologic malignancy predisposition syndrome.

What condition is associated with DDX41 p.Phe535fs (c.1603_1605delinsA)?

DDX41 p.Phe535fs (c.1603_1605delinsA) is associated with DDX41-related hematologic malignancy predisposition syndrome (ClinVar).

How common is DDX41 p.Phe535fs (c.1603_1605delinsA) in the general population?

DDX41 p.Phe535fs (c.1603_1605delinsA) is absent from gnomAD (gnomAD).

DDX41 p.Phe535fs

Q: How is DDX41-related hematologic malignancy predisposition syndrome inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

c.1603_1605delinsA · rs2532074787 · VCV2500216

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

DDX41-related hematologic malignancy predisposition syndrome

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 15 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP 0.18, 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.Phe535fs
Coding: c.1603_1605delinsA
MANE Select: NM_016222
dbSNP: rs2532074787
Type: Indel
Location: chr5:177512338 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 535: the helicase c-terminal domain; a β-strand

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

Disease context

DDX41-related hematologic malignancy predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DDX41-related hematologic malignancy predisposition syndrome (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

DDX41 c.435-2_435-1delinsCA Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Phe535Ile Uncertain significance ★ ⚠ same residue
DDX41 p.Phe535= Likely benign ★ same residue
DDX41 c.434+1G>A Pathogenic/Likely pathogenic ★★ same condition
DDX41 c.434+1G>C Pathogenic/Likely pathogenic ★★ same condition
DDX41 c.935+1G>T Likely pathogenic ★★ same condition
DDX41 p.Ala500fs Pathogenic ★★ same condition
DDX41 p.Arg159Ter 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-phe535fs (accessed [today's date]).

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