DDX41 p.Lys442=
c.1326G>A · VCV3716821
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.42 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 7.384 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/60,028 alleles
Filtering AF
0.00899%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00173%
28/1,614,056 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,003 |
| East Asian | 0.00223% | 44,886 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.00136% | 73,751 |
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.Lys442=
- Coding
- c.1326G>A
- MANE Select
- NM_016222
- Type
- single nucleotide variant
- Location
- chr5:177512853 (GRCh38)
- Gene constraint
- LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.38 · 5 PDB
- Residue 442
- a cross-link site; the helicase c-terminal domain; an α-helix
Similar variants
- DDX41 p.Lys442Glu Uncertain significance ★ ⚠ same residue
- DDX41 p.Lys442Thr 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
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-lys442 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown