Is DICER1 p.Ile1663= (c.4989A>T) pathogenic?

DICER1 p.Ile1663= (c.4989A>T) is classified Likely benign in DICER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-23). Very rare (popmax 8.47e-05%, nfe); Associated with DICER1-related tumor predisposition.

What condition is associated with DICER1 p.Ile1663= (c.4989A>T)?

DICER1 p.Ile1663= (c.4989A>T) is associated with DICER1-related tumor predisposition (ClinVar).

How common is DICER1 p.Ile1663= (c.4989A>T) in the general population?

DICER1 p.Ile1663= (c.4989A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is DICER1 tumor-predisposition syndrome inherited?

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

DICER1 p.Ile1663=

c.4989A>T · VCV4780970

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

DICER1-related tumor predisposition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.528	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -3.5, phastCons 1
Overall
CADD	3.719	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.2e-05% 1/1,614,198 alleles · very rare exomes 1/1,461,880 · genomes 0/152,318 · joint denominator

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.Ile1663=
Coding: c.4989A>T
MANE Select: NM_177438
Type: single nucleotide variant
Location: chr14:95095931 (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

DICER1-related tumor predisposition — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.Ile1663fs Pathogenic ★★ same residue
DICER1 p.Ile1663Leu 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

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-ile1663 (accessed [today's date]).

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