Is DDX41 p.Pro189Ser (c.565C>T) pathogenic?

DDX41 p.Pro189Ser (c.565C>T) is classified Uncertain significance in DDX41 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-30). AlphaMissense: likely pathogenic (0.6262); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with DDX41 p.Pro189Ser (c.565C>T)?

DDX41 p.Pro189Ser (c.565C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DDX41 p.Pro189Ser (c.565C>T) in the general population?

DDX41 p.Pro189Ser (c.565C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about DDX41 p.Pro189Ser (c.565C>T)?

AlphaMissense predicts likely pathogenic (score 0.6262) — an in-silico prediction, not a clinical call.

DDX41 p.Pro189Ser

c.565C>T · rs1450576850 · VCV1928110

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6262 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6262	likely pathogenic
REVEL	0.384	indeterminate
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 907 bp · p 0.33 · regional, not allelic
Overall
CADD	29.5	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 0.00329% South Asian · 3/91,082 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000806% 13/1,613,896 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Admixed American	0.00167%	59,990
African / African-American	0.00134%	74,906
European (non-Finnish)	0.000678%	147,500

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.Pro189Ser
Coding: c.565C>T
MANE Select: NM_016222
dbSNP: rs1450576850
Type: single nucleotide variant
Location: chr5:177515691 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB

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.Pro189Leu 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
DDX41 p.Arg159Ter 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-pro189ser (accessed [today's date]).

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