Is DDX41 p.Pro499fs (c.1496del) pathogenic?

DDX41 p.Pro499fs (c.1496del) is classified Pathogenic/Likely pathogenic in DDX41 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-14). No gnomAD frequency available for this variant; Associated with Inborn genetic diseases.

What condition is associated with DDX41 p.Pro499fs (c.1496del)?

DDX41 p.Pro499fs (c.1496del) is associated with Inborn genetic diseases, DDX41-related hematologic malignancy predisposition syndrome (ClinVar).

How common is DDX41 p.Pro499fs (c.1496del) in the general population?

DDX41 p.Pro499fs (c.1496del) is no gnomAD frequency available for this variant (gnomAD).

DDX41 p.Pro499fs

c.1496del · rs753425379 · VCV2674795

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

Inborn genetic diseases

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 0.86	GERP -0.88, phastCons 0.98

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.Pro499fs
Coding: c.1496del
MANE Select: NM_016222
dbSNP: rs753425379
Type: Deletion
Location: chr5:177512549 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 499: the helicase c-terminal domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: DDX41-related hematologic malignancy predisposition syndrome

Similar variants

DDX41 p.Pro499Leu Uncertain significance ★ ⚠ same residue
DDX41 p.Pro499= Likely benign ★ same residue
DDX41 p.Glu268fs Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Glu60fs Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Gly465fs Pathogenic ★★ same condition
DDX41 p.Ile209fs Pathogenic ★★ same condition
DDX41 p.Leu283fs Pathogenic/Likely pathogenic ★★ same condition
DDX41 p.Lys102fs 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-pro499fs (accessed [today's date]).

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