Is DDX41 p.Leu341= (c.1021C>T) pathogenic?

DDX41 p.Leu341= (c.1021C>T) is classified Likely benign in DDX41 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-17). Very rare (popmax 0.000847%, nfe); Associated with DDX41-related hematologic malignancy predisposition syndrome.

What condition is associated with DDX41 p.Leu341= (c.1021C>T)?

DDX41 p.Leu341= (c.1021C>T) is associated with DDX41-related hematologic malignancy predisposition syndrome (ClinVar).

How common is DDX41 p.Leu341= (c.1021C>T) in the general population?

DDX41 p.Leu341= (c.1021C>T) is very rare (popmax 0.000847%, nfe) (gnomAD).

DDX41 p.Leu341=

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.1021C>T · VCV3766666

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Conditions

DDX41-related hematologic malignancy predisposition syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.1, phastCons 1
Overall
CADD	9.495	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,180,030 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,613,766 alleles · very rare

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: DDX41
Protein: p.Leu341=
Coding: c.1021C>T
MANE Select: NM_016222
Type: single nucleotide variant
Location: chr5:177513762 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 341: the helicase atp-binding 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 p.Leu341Pro Uncertain significance ★ ⚠ same residue
DDX41 p.Leu341Val Uncertain significance ★ ⚠ 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-leu341 (accessed [today's date]).

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