Is WT1 p.Val384= (c.1152A>G) pathogenic?

WT1 p.Val384= (c.1152A>G) is classified Likely benign in WT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-01). Very rare (popmax 0.00133%, afr); Associated with Denys-Drash syndrome.

What condition is associated with WT1 p.Val384= (c.1152A>G)?

WT1 p.Val384= (c.1152A>G) is associated with Denys-Drash syndrome, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Val384= (c.1152A>G) in the general population?

WT1 p.Val384= (c.1152A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Denys-Drash syndrome inherited?

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

WT1 p.Val384=

c.1152A>G · rs2132941316 · VCV1086647

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Denys-Drash syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.073	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -5.4, phastCons 0.86
Overall
CADD	3.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,028 alleles

Overall 6.2e-05% 1/1,614,080 alleles · very rare exomes 1/1,461,858 · genomes 0/152,222 · 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: WT1
Protein: p.Val384=
Coding: c.1152A>G
MANE Select: NM_024426
dbSNP: rs2132941316
Type: single nucleotide variant
Location: chr11:32396369 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB

Full WT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Denys-Drash syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Frasier syndrome Wilms tumor 1 WAGR syndrome

For Denys-Drash syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

WT1 p.Val384Ile Conflicting classifications of pathogenicity ★ same residue
WT1 p.Val384fs Pathogenic ★ same residue
WT1 p.Val384_Arg385insThrLeuVal Uncertain significance ★ same residue
WT1 c.1354+2T>C Pathogenic/Likely pathogenic ★★ same condition
WT1 c.1447+2T>C Pathogenic ★★ same condition
WT1 c.1447+4C>T Pathogenic/Likely pathogenic ★★ same condition
WT1 c.1447+5G>A Pathogenic/Likely pathogenic ★★ same condition
WT1 c.1448-1G>A Pathogenic/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/wt1-p-val384 (accessed [today's date]).

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