Is DROSHA p.Ile1344= (c.4032C>T) pathogenic?

DROSHA p.Ile1344= (c.4032C>T) is classified Likely benign in DROSHA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-01-10). Rare (popmax 0.155%, afr); Associated with DROSHA-related disorder.

What condition is associated with DROSHA p.Ile1344= (c.4032C>T)?

DROSHA p.Ile1344= (c.4032C>T) is associated with DROSHA-related disorder (ClinVar).

How common is DROSHA p.Ile1344= (c.4032C>T) in the general population?

DROSHA p.Ile1344= (c.4032C>T) is rare (popmax 0.155%, afr) (gnomAD).

DROSHA p.Ile1344=

c.4032C>T · rs200996611 · VCV3057415

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.155%, afr)

Conditions

DROSHA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP -2.1, phastCons 1
Overall
CADD	7.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.155% African / African-American · 116/74,646 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0102% 164/1,604,014 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.155%	644
Middle Eastern	0.0831%	1,204
Remaining individualsnot grpmax-eligible	0.0145%	6,882
Admixed American	0.0119%	8,395
East Asian	0.00676%	14,803
South Asian	0.00447%	22,382
European (non-Finnish)	0.0017%	58,748

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.Ile1344=
Coding: c.4032C>T
MANE Select: NM_001382508
dbSNP: rs200996611
Type: single nucleotide variant
Location: chr5:31401525 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.94 · 12 PDB
Residue 1344: 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-ile1344 (accessed [today's date]).

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