Is DROSHA p.Pro1102= (c.3306A>G) pathogenic?

DROSHA p.Pro1102= (c.3306A>G) is classified Benign in DROSHA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-30). Common (popmax 70.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with DROSHA-related disorder.

What condition is associated with DROSHA p.Pro1102= (c.3306A>G)?

DROSHA p.Pro1102= (c.3306A>G) is associated with DROSHA-related disorder (ClinVar).

DROSHA p.Pro1102=

Q: How common is DROSHA p.Pro1102= (c.3306A>G) in the general population?

DROSHA p.Pro1102= (c.3306A>G) is common (popmax 70.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3306A>G · rs2287584 · VCV3060707

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 70.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

DROSHA-related disorder

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 -1.3	GERP -3.2, phastCons 0.001
Overall
CADD	2.261	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.4% East Asian · 31,508/44,784 alleles

Filtering AF 69.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 69.4%

Overall 26% 418,156/1,610,786 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	70.4%	1
African / African-American	52.4%	2
South Asian	36.8%	3
Admixed American	33.7%	3
Middle Eastern	33.2%	3
Ashkenazi Jewishnot grpmax-eligible	30%	3
Remaining individualsnot grpmax-eligible	28.9%	3
Amishnot grpmax-eligible	28.7%	3
Finnishnot grpmax-eligible	25.1%	4
European (non-Finnish)	21.1%	5

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.Pro1102=
Coding: c.3306A>G
MANE Select: NM_001382508
dbSNP: rs2287584
Type: single nucleotide variant
Location: chr5:31422900 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.94 · 12 PDB
Residue 1102: an α-helix; the 'necessary for interaction with dgcr8 and pri-mirna processing activity' region

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

Disease context

DROSHA-related disorder

Similar variants

DROSHA p.Arg234Ter Uncertain significance ★★ same condition
DROSHA p.Asp248His Uncertain significance ★★ ⚠ same condition
DROSHA p.Pro100Leu Uncertain significance ★★ ⚠ same condition
DROSHA p.Arg287Ter Uncertain significance ★ same condition
DROSHA p.Arg354Cys Uncertain significance ★ ⚠ same condition
DROSHA p.Arg40Thr Uncertain significance ★ ⚠ same condition
DROSHA p.Asp1219Gly Uncertain significance ★ ⚠ same condition
DROSHA p.Pro211Thr Uncertain significance ★ ⚠ 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/drosha-p-pro1102 (accessed [today's date]).

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