Is DICER1 p.Asp305= (c.915C>T) pathogenic?

DICER1 p.Asp305= (c.915C>T) is classified Conflicting classifications of pathogenicity in DICER1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-09-29). Very rare (popmax 0.0011%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with DICER1 p.Asp305= (c.915C>T)?

DICER1 p.Asp305= (c.915C>T) is associated with hereditary neoplastic syndrome, DICER1-related tumor predisposition (ClinVar).

How common is DICER1 p.Asp305= (c.915C>T) in the general population?

DICER1 p.Asp305= (c.915C>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

DICER1 p.Asp305=

c.915C>T · rs886050944 · VCV315111

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

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 4.6	GERP 1.8, phastCons 1
Overall
CADD	8.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,178,918 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00089% 13/1,460,094 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.Asp305=
Coding: c.915C>T
MANE Select: NM_177438
dbSNP: rs886050944
Type: single nucleotide variant
Location: chr14:95124657 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 67.89 · 21 PDB
Residue 305: 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

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

Also linked: DICER1-related tumor predisposition

Similar variants

DICER1 p.Asp305Tyr Uncertain significance ★★ ⚠ same residue
DICER1 p.Asp305Glu Uncertain significance ★ ⚠ same residue
DICER1 p.Asp305fs Pathogenic ★ 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-asp305 (accessed [today's date]).

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