Is DICER1 p.Ala1326Val (c.3977C>T) pathogenic?

DICER1 p.Ala1326Val (c.3977C>T) is classified Uncertain significance in DICER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-20). AlphaMissense: likely pathogenic (0.9405); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with DICER1 p.Ala1326Val (c.3977C>T)?

DICER1 p.Ala1326Val (c.3977C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is DICER1 p.Ala1326Val (c.3977C>T) in the general population?

DICER1 p.Ala1326Val (c.3977C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DICER1 p.Ala1326Val (c.3977C>T)?

AlphaMissense predicts likely pathogenic (score 0.9405) — an in-silico prediction, not a clinical call.

DICER1 p.Ala1326Val

c.3977C>T · rs2139955138 · VCV1736655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9405 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9405	likely pathogenic
REVEL	0.65	pathogenic-leaning
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 3,702 bp · p 1.6e-09 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DICER1
Protein: p.Ala1326Val
Coding: c.3977C>T
MANE Select: NM_177438
dbSNP: rs2139955138
Type: single nucleotide variant
Location: chr14:95103419 (GRCh38)
Gene constraint: LOEUF 0.275 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 67.89 · 21 PDB
Residue 1326: an α-helix; the rnase iii 1 domain

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

Similar variants

DICER1 p.Ala1326Thr Uncertain significance ★★ ⚠ same residue
DICER1 p.Ala1326= Likely benign ★ same residue
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>C Likely pathogenic ★★★ same condition
DICER1 c.2257-7A>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-ala1326val (accessed [today's date]).

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