Is DDX41 p.Pro561Ser (c.1681C>T) pathogenic?

DDX41 p.Pro561Ser (c.1681C>T) is classified Uncertain significance in DDX41 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). AlphaMissense: likely benign (0.1206); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DDX41 p.Pro561Ser (c.1681C>T)?

DDX41 p.Pro561Ser (c.1681C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DDX41 p.Pro561Ser (c.1681C>T) in the general population?

DDX41 p.Pro561Ser (c.1681C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX41 p.Pro561Ser (c.1681C>T)?

AlphaMissense predicts likely benign (score 0.1206) — an in-silico prediction, not a clinical call.

DDX41 p.Pro561Ser

c.1681C>T · VCV3500527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1206 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1206	likely benign
REVEL	0.404	indeterminate
SaProt	LLR -7.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 1,932 bp · p 1.8e-21 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Pro561Ser
Coding: c.1681C>T
MANE Select: NM_016222
Type: single nucleotide variant
Location: chr5:177512147 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 561: the helicase c-terminal domain; an α-helix

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

Similar variants

DDX41 p.Pro561Leu Uncertain significance ★★ ⚠ same residue
DDX41 p.Pro561= Likely benign ★ same residue
DDX41 c.1303-2A>G Likely pathogenic ★★ same condition
DDX41 c.27+1G>A Likely pathogenic ★★ same condition
DDX41 c.434+1G>C Pathogenic/Likely pathogenic ★★ same condition
DDX41 c.571+1G>A Likely pathogenic ★★ same condition
DDX41 c.572-1G>A Pathogenic/Likely 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-pro561ser (accessed [today's date]).

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