Is DDX41 p.Pro35Arg (c.104C>G) pathogenic?

DDX41 p.Pro35Arg (c.104C>G) is classified Uncertain significance in DDX41 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-15). AlphaMissense: likely pathogenic (0.7083); Ultra-rare (popmax 0.0491%, eas); Associated with Inborn genetic diseases.

What condition is associated with DDX41 p.Pro35Arg (c.104C>G)?

DDX41 p.Pro35Arg (c.104C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DDX41 p.Pro35Arg (c.104C>G) in the general population?

DDX41 p.Pro35Arg (c.104C>G) is ultra-rare (popmax 0.0491%, eas) (gnomAD).

What do computational predictors say about DDX41 p.Pro35Arg (c.104C>G)?

AlphaMissense predicts likely pathogenic (score 0.7083) — an in-silico prediction, not a clinical call.

DDX41 p.Pro35Arg

c.104C>G · rs984823447 · VCV2980765

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7083 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7083	likely pathogenic
REVEL	0.267	benign-leaning
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 610 bp · p 0.021 · regional, not allelic
Overall
CADD	27.4	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 0.0491% East Asian · 22/44,812 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.028%

Overall 0.00137% 22/1,611,366 alleles · ultra-rare exomes 22/1,459,010 · genomes 0/152,356 · joint denominator

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.Pro35Arg
Coding: c.104C>G
MANE Select: NM_016222
dbSNP: rs984823447
Type: single nucleotide variant
Location: chr5:177516759 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 35: 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.Pro35Leu Uncertain significance ★★ ⚠ same residue
DDX41 p.Pro35= Likely benign ★ same residue
DDX41 p.Pro35Ala 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-pro35arg (accessed [today's date]).

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