Is DICER1 p.Pro430= (c.1290A>G) pathogenic?

DICER1 p.Pro430= (c.1290A>G) is classified Likely benign in DICER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with DICER1 p.Pro430= (c.1290A>G)?

DICER1 p.Pro430= (c.1290A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is DICER1 p.Pro430= (c.1290A>G) in the general population?

DICER1 p.Pro430= (c.1290A>G) is absent from gnomAD v4.1 (gnomAD).

DICER1 p.Pro430=

c.1290A>G · VCV4636924

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 0.064	GERP -0.64, phastCons 0.97
Overall
CADD	7.574	PHRED · no single calibrated threshold — expert panels disagree

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: DICER1
Protein: p.Pro430=
Coding: c.1290A>G
MANE Select: NM_177438
Type: single nucleotide variant
Location: chr14:95124282 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 67.89 · 21 PDB
Residue 430: the 'required for interaction with prkra and tarbp2' region; the 'disordered' region

Full DICER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DICER1 p.Pro430Ser Uncertain significance ★★ ⚠ same residue
DICER1 p.Pro430Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
DICER1 p.Pro430Leu Uncertain significance ★ ⚠ same residue
DICER1 c.1752+213A>G Likely pathogenic ★★★ same condition
DICER1 c.1753-9A>G Likely pathogenic ★★★ same condition
DICER1 c.1907+1G>A Pathogenic ★★★ same condition
DICER1 c.1908-3C>G Likely pathogenic ★★★ same condition
DICER1 c.2256+5G>C Likely pathogenic ★★★ 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/dicer1-p-pro430 (accessed [today's date]).

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