DDX41 p.Pro321=
c.963G>A · rs200664784 · VCV2674770
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00801%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.45 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.22 | GERP -4.8, phastCons 0.002 |
| Overall | ||
| CADD | 17.89 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00801%
African / African-American · 6/74,902 alleles
Filtering AF
0.00347%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00229%
Overall
0.00291%
47/1,613,532 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00801% | 12,484 |
| East Asian | 0.00446% | 22,446 |
| European (non-Finnish) | 0.00297% | 33,714 |
| South Asian | 0.0022% | 45,542 |
| Admixed American | 0.00167% | 59,998 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
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.Pro321=
- Coding
- c.963G>A
- MANE Select
- NM_016222
- dbSNP
- rs200664784
- Type
- single nucleotide variant
- Location
- chr5:177513820 (GRCh38)
- Gene constraint
- LOEUF 0.768 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.38 · 5 PDB
- Residue 321
- the helicase atp-binding domain; an α-helix
Similar variants
- DDX41 p.Pro321Gln Uncertain significance ★ ⚠ same residue
- DDX41 p.Pro321Leu 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>A Pathogenic/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-pro321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown