Is DDX41 p.Ser266= (c.798G>A) pathogenic?

DDX41 p.Ser266= (c.798G>A) is classified Conflicting classifications of pathogenicity in DDX41 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-05-21). Very rare (popmax 0.00224%, eas); Associated with DDX41-related hematologic malignancy predisposition syndrome.

What condition is associated with DDX41 p.Ser266= (c.798G>A)?

DDX41 p.Ser266= (c.798G>A) is associated with DDX41-related hematologic malignancy predisposition syndrome (ClinVar).

How common is DDX41 p.Ser266= (c.798G>A) in the general population?

DDX41 p.Ser266= (c.798G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

DDX41 p.Ser266=

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.798G>A · rs750013130 · VCV3241293

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

DDX41-related hematologic malignancy predisposition syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.52	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.87	GERP -3.9, phastCons 0.003
Overall
CADD	17.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,566 alleles

Filtering AF 0.000769% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00061%

Overall 0.00118% 19/1,603,506 alleles · very rare exomes 17/1,451,322 · genomes 2/152,184 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,566
South Asian	0.0022%	45,486
African / African-American	0.00134%	74,718
European (non-Finnish)	0.00128%	78,104

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.Ser266=
Coding: c.798G>A
MANE Select: NM_016222
dbSNP: rs750013130
Type: single nucleotide variant
Location: chr5:177514916 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 266: the helicase atp-binding domain

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.Ser266Leu 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
DDX41 p.Gln370Ter 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-ser266 (accessed [today's date]).

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