Is DDX41 p.Asp467Glu (c.1401C>G) pathogenic?

DDX41 p.Asp467Glu (c.1401C>G) is classified Uncertain significance in DDX41 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). AlphaMissense: likely pathogenic (0.6969); Absent from gnomAD v4.1.

How common is DDX41 p.Asp467Glu (c.1401C>G) in the general population?

DDX41 p.Asp467Glu (c.1401C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDX41 p.Asp467Glu (c.1401C>G)?

AlphaMissense predicts likely pathogenic (score 0.6969) — an in-silico prediction, not a clinical call.

DDX41 p.Asp467Glu

c.1401C>G · VCV3368782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6969	likely pathogenic
REVEL	0.553	indeterminate
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Pangolin	Δ0.32	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 1,932 bp · p 1.8e-21 · regional, not allelic
Overall
CADD	23.4	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

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.Asp467Glu
Coding: c.1401C>G
MANE Select: NM_016222
Type: single nucleotide variant
Location: chr5:177512644 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 5 PDB
Residue 467: the helicase c-terminal domain

Full DDX41 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX41 c.1098+2T>G Likely pathogenic ★★ same type
DDX41 c.1303-2A>G Likely pathogenic ★★ same type
DDX41 c.27+1G>A Likely pathogenic ★★ same type
DDX41 c.434+1G>A Pathogenic/Likely pathogenic ★★ same type
DDX41 c.434+1G>C Pathogenic/Likely pathogenic ★★ same type
DDX41 c.571+1G>A Likely pathogenic ★★ same type
DDX41 c.572-1G>A Pathogenic/Likely pathogenic ★★ same type
DDX41 c.935+1G>T Likely pathogenic ★★ same type

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-asp467glu (accessed [today's date]).

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