Is DDX41 p.Pro17Arg (c.50C>G) pathogenic?

DDX41 p.Pro17Arg (c.50C>G) is classified Conflicting classifications of pathogenicity in DDX41 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-02). AlphaMissense: likely benign (0.0854); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DDX41 p.Pro17Arg (c.50C>G)?

DDX41 p.Pro17Arg (c.50C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DDX41 p.Pro17Arg (c.50C>G) in the general population?

DDX41 p.Pro17Arg (c.50C>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about DDX41 p.Pro17Arg (c.50C>G)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

DDX41 p.Pro17Arg

c.50C>G · rs1761259465 · VCV2748222

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -0.3, phastCons 0.98
Regional constraint	o/e 1.22	unconstrained · MANE · 610 bp · p 0.021 · regional, not allelic
Overall
CADD	18.17	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

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,848 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000548% 8/1,460,202 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.Pro17Arg
Coding: c.50C>G
MANE Select: NM_016222
dbSNP: rs1761259465
Type: single nucleotide variant
Location: chr5:177516813 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 17: the 'disordered' region

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.Pro17= Likely benign ★★ same residue
DDX41 p.Pro17Leu Uncertain significance ★ ⚠ same residue
DDX41 p.Pro17Ser Uncertain significance ★ ⚠ 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

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-pro17arg (accessed [today's date]).

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