Is DICER1 p.Phe363= (c.1089C>T) pathogenic?

DICER1 p.Phe363= (c.1089C>T) is classified Likely benign in DICER1 (ClinVar, Expert panel, 5 submitters; last evaluated 2024-04-23). Very rare (popmax 0.000137%); Associated with DICER1-related tumor predisposition.

What condition is associated with DICER1 p.Phe363= (c.1089C>T)?

DICER1 p.Phe363= (c.1089C>T) is associated with DICER1-related tumor predisposition, hereditary neoplastic syndrome (ClinVar).

How common is DICER1 p.Phe363= (c.1089C>T) in the general population?

DICER1 p.Phe363= (c.1089C>T) is very rare (popmax 0.000137%) (gnomAD).

How is DICER1 tumor-predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

DICER1 p.Phe363=

c.1089C>T · rs878855239 · VCV242030

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Conditions

DICER1-related tumor predisposition

ClinGen expert panel — DICER1 and miRNA-Processing Gene VCEP

Likely Benign for DICER1-related tumor predisposition. Applied ACMG criteria (verbatim):

BP7 BP4

Curation rationale (ClinGen, verbatim)

The NM_177438.3:c.1089C>T (p.Phe363=) variant is a synonymous (silent) variant that is not predicted to impact splicing by MaxEntScan or SpliceAI (BP4, BP7). The total allele frequency in gnomAD v4.1.0 is 0.000001368 (2/1461842 alleles) with a highest population minor allele frequency of 0.00003312 (2/60394 alleles) in a population of undisclosed ancestry (PM2_Supporting, BS1, and BA1 are not met). In summary, this variant meets the criteria to be classified as Likely Benign for DICER1-related tumor predisposition based on the ACMG/AMP criteria applied, as specified by the ClinGen DICER1 VCEP: BP4, BP7. (Bayesian Points: -2; VCEP specifications version 1.3.0; 04/23/2024)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 12	GERP 1.8, phastCons 1
Overall
CADD	13.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000137%

Overall 0.000137% 2/1,461,842 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: DICER1
Protein: p.Phe363=
Coding: c.1089C>T
MANE Select: NM_177438
dbSNP: rs878855239
Type: single nucleotide variant
Location: chr14:95124483 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 67.89 · 21 PDB
Residue 363: a β-strand; the 'required for interaction with prkra and tarbp2' region

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

Disease context

Also linked: hereditary neoplastic syndrome

For DICER1 tumor-predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

DICER1 p.Phe363Ile Uncertain significance ★ ⚠ same residue
DICER1 p.Phe363Leu Uncertain significance ★ ⚠ same residue
DICER1 p.Phe363_Ser364delinsLeuPro Uncertain significance ★ same residue
DICER1 c.1509+16A>G Likely pathogenic ★★★ same condition
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

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-phe363 (accessed [today's date]).

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