Is DICER1 p.Ile1663fs (c.4984del) pathogenic?

DICER1 p.Ile1663fs (c.4984del) is classified Pathogenic in DICER1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-08). Absent from gnomAD; Associated with DICER1-related tumor predisposition.

What condition is associated with DICER1 p.Ile1663fs (c.4984del)?

DICER1 p.Ile1663fs (c.4984del) is associated with DICER1-related tumor predisposition, hereditary neoplastic syndrome (ClinVar).

How common is DICER1 p.Ile1663fs (c.4984del) in the general population?

DICER1 p.Ile1663fs (c.4984del) is absent from gnomAD (gnomAD).

How is DICER1 tumor-predisposition syndrome inherited?

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

DICER1 p.Ile1663fs

c.4984del · rs1131691196 · VCV429121

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

DICER1-related tumor predisposition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 23 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DICER1
Protein: p.Ile1663fs
Coding: c.4984del
MANE Select: NM_177438
dbSNP: rs1131691196
Type: Deletion
Location: chr14:95095936 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 67.89 · 21 PDB
Residue 1663: a turn

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.Ile1663Met Uncertain significance ★★ ⚠ same residue
DICER1 p.Ile1663Thr Uncertain significance ★★ ⚠ same residue
DICER1 p.Ile1663Val Uncertain significance ★★ ⚠ same residue
DICER1 p.Ile1663Leu Uncertain significance ★ ⚠ same residue
DICER1 p.Ile1663= Likely benign ★ same residue
DICER1 p.Arg293fs Pathogenic ★★★ same condition
DICER1 p.Glu292fs Likely pathogenic ★★★ same condition
DICER1 p.Ile627fs 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-ile1663fs (accessed [today's date]).

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