DROSHA p.Ala1050=
c.3150T>A · rs368428431 · VCV739822
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, 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 0.93 | GERP 1.7, phastCons 0.98 |
| Overall | ||
| CADD | 9.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,976 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000137%
2/1,459,194 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
- DROSHA
- Protein
- p.Ala1050=
- Coding
- c.3150T>A
- MANE Select
- NM_001382508
- dbSNP
- rs368428431
- Type
- single nucleotide variant
- Location
- chr5:31429541 (GRCh38)
- Gene constraint
- LOEUF 0.39 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.94 · 12 PDB
- Residue 1050
- the rnase iii 1 domain; an α-helix; 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.Ile1309= Benign ★★ same type
- DROSHA p.Leu1009= Benign ★★ same type
- DROSHA p.Lys388= 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-ala1050 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown