Is DDX41 p.Pro78Ser (c.232C>T) pathogenic?

DDX41 p.Pro78Ser (c.232C>T) is classified Likely benign in DDX41 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1066); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DDX41 p.Pro78Ser (c.232C>T)?

DDX41 p.Pro78Ser (c.232C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DDX41 p.Pro78Ser (c.232C>T) in the general population?

DDX41 p.Pro78Ser (c.232C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DDX41 p.Pro78Ser (c.232C>T)?

AlphaMissense predicts likely benign (score 0.1066) — an in-silico prediction, not a clinical call.

DDX41 p.Pro78Ser

c.232C>T · VCV4617162

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1066 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1066	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -6.54	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 12	GERP 0.88, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 610 bp · p 0.021 · regional, not allelic
Overall
CADD	22.8	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.84e-05% 1/1,461,778 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.Pro78Ser
Coding: c.232C>T
MANE Select: NM_016222
Type: single nucleotide variant
Location: chr5:177516354 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 78: 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.Pro78Leu Uncertain significance ★★ ⚠ same residue
DDX41 p.Pro78= Likely benign ★ same residue
DDX41 p.Pro78Ala 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

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-pro78ser (accessed [today's date]).

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