Is DROSHA p.Phe572Val (c.1714T>G) pathogenic?

DROSHA p.Phe572Val (c.1714T>G) is classified Uncertain significance in DROSHA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). AlphaMissense: likely pathogenic (0.7775); Absent from gnomAD v4.1.

How common is DROSHA p.Phe572Val (c.1714T>G) in the general population?

DROSHA p.Phe572Val (c.1714T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DROSHA p.Phe572Val (c.1714T>G)?

AlphaMissense predicts likely pathogenic (score 0.7775) — an in-silico prediction, not a clinical call.

DROSHA p.Phe572Val

c.1714T>G · VCV4014878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7775	likely pathogenic
REVEL	0.284	benign-leaning
SaProt	LLR -9.90	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 83 kb · p 1.4e-29 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DROSHA
Protein: p.Phe572Val
Coding: c.1714T>G
MANE Select: NM_001382508
Type: single nucleotide variant
Location: chr5:31495327 (GRCh38)
Gene constraint: LOEUF 0.39 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.94 · 12 PDB
Residue 572: the 'necessary for interaction with dgcr8 and pri-mirna processing activity' region; a β-strand

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

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-phe572val (accessed [today's date]).

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