Is DICER1 p.Ser299= (c.897G>A) pathogenic?

DICER1 p.Ser299= (c.897G>A) is classified Conflicting classifications of pathogenicity in DICER1 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-04-15). Ultra-rare (popmax 0.0178%, mid); Associated with DICER1-related tumor predisposition.

What condition is associated with DICER1 p.Ser299= (c.897G>A)?

DICER1 p.Ser299= (c.897G>A) is associated with DICER1-related tumor predisposition, hereditary neoplastic syndrome (ClinVar).

How common is DICER1 p.Ser299= (c.897G>A) in the general population?

DICER1 p.Ser299= (c.897G>A) is ultra-rare (popmax 0.0178%, mid) (gnomAD).

How is DICER1 tumor-predisposition syndrome inherited?

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

DICER1 p.Ser299=

c.897G>A · rs201842071 · VCV315112

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, mid)

Conditions

DICER1-related tumor predisposition

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 0.77	GERP -2.9, phastCons 0.97
Overall
CADD	9.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% Middle Eastern · 1/5,608 alleles

Filtering AF 0.00492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00452%

Overall 0.00483% 73/1,512,622 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0178%	5,608
European (non-Finnish)	0.00615%	16,249
Remaining individualsnot grpmax-eligible	0.00508%	19,679
East Asian	0.00226%	44,264
Admixed American	0.00167%	59,806

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.Ser299=
Coding: c.897G>A
MANE Select: NM_177438
dbSNP: rs201842071
Type: single nucleotide variant
Location: chr14:95126586 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 67.89 · 21 PDB
Residue 299: an α-helix; 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.Ser299Leu Conflicting classifications of pathogenicity ★ ⚠ 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
DICER1 c.2256+5G>A 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-ser299 (accessed [today's date]).

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