Is DDX41 p.Pro179Ser (c.535C>T) pathogenic?

DDX41 p.Pro179Ser (c.535C>T) is classified Conflicting classifications of pathogenicity in DDX41 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-10). AlphaMissense: likely pathogenic (0.9481); Absent from gnomAD v4.1; Associated with DDX41-related hematologic malignancy predisposition syndrome.

What condition is associated with DDX41 p.Pro179Ser (c.535C>T)?

DDX41 p.Pro179Ser (c.535C>T) is associated with DDX41-related hematologic malignancy predisposition syndrome (ClinVar).

How common is DDX41 p.Pro179Ser (c.535C>T) in the general population?

DDX41 p.Pro179Ser (c.535C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX41 p.Pro179Ser (c.535C>T)?

AlphaMissense predicts likely pathogenic (score 0.9481) — an in-silico prediction, not a clinical call.

DDX41 p.Pro179Ser

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.535C>T · VCV3899314

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9481 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DDX41-related hematologic malignancy predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.9481	likely pathogenic
REVEL	0.352	indeterminate
SaProt	LLR -14.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 907 bp · p 0.33 · regional, not allelic
Overall
CADD	29.5	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: DDX41
Protein: p.Pro179Ser
Coding: c.535C>T
MANE Select: NM_016222
Type: single nucleotide variant
Location: chr5:177515721 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 179: an α-helix

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 p.Pro179fs Likely pathogenic ★ same residue
DDX41 p.Pro179= 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.Arg159Ter Pathogenic ★★ same condition
DDX41 p.Arg311Ter Pathogenic ★★ same condition
DDX41 p.Arg369Ter 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-pro179ser (accessed [today's date]).

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