DROSHA p.Ile1309=
c.3927A>C · rs147180304 · VCV789582
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.948%, afr)
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 1.1 | GERP 0.28, phastCons 1 |
| Overall | ||
| CADD | 6.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.948%
African / African-American · 711/75,028 alleles
Filtering AF
0.89%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.867%
Overall
0.0499%
806/1,613,778 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.948% | 106 |
| Admixed American | 0.0833% | 1,200 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,562 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.00017% | 589,859 |
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
- DROSHA
- Protein
- p.Ile1309=
- Coding
- c.3927A>C
- MANE Select
- NM_001382508
- dbSNP
- rs147180304
- Type
- single nucleotide variant
- Location
- chr5:31406873 (GRCh38)
- Gene constraint
- LOEUF 0.39 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.94 · 12 PDB
- Residue 1309
- a β-strand; the drbm domain; the 'necessary for interaction with dgcr8 and pri-mirna processing activity' region
Similar variants
- DROSHA p.Arg234Ter Uncertain significance ★★ same type
- DROSHA p.Asp248His Uncertain significance ★★ ⚠ same type
- DROSHA p.Lys1373Glu Uncertain significance ★★ ⚠ same type
- DROSHA p.Pro100Leu Uncertain significance ★★ ⚠ same type
- DROSHA c.3216+9A>G Benign ★★ same type
- DROSHA p.Leu1009= Benign ★★ same type
- DROSHA p.Lys388= Benign ★★ same type
- DROSHA p.Pro56Ser Likely benign ★★ 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/drosha-p-ile1309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown