Is WT1 p.Val373= (c.1119G>A) pathogenic?

WT1 p.Val373= (c.1119G>A) is classified Likely benign in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-14). Very rare (popmax 0.00329%, sas); Associated with Wilms tumor 1.

What condition is associated with WT1 p.Val373= (c.1119G>A)?

WT1 p.Val373= (c.1119G>A) is associated with Wilms tumor 1, Frasier syndrome, WAGR syndrome (ClinVar).

How common is WT1 p.Val373= (c.1119G>A) in the general population?

WT1 p.Val373= (c.1119G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

WT1 p.Val373=

c.1119G>A · rs780497248 · VCV1109384

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Wilms tumor 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.117	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.29	GERP -3.1, phastCons 0.14
Overall
CADD	3.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,070 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,613,872 alleles · very rare exomes 3/1,461,576 · genomes 0/152,296 · 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.Val373=
Coding: c.1119G>A
MANE Select: NM_024426
dbSNP: rs780497248
Type: single nucleotide variant
Location: chr11:32396402 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 373: a UniProt-annotated variant site (in dds and wt1); a UniProt-annotated variant site (in dds); the 'important for interaction with target dna' region; an α-helix

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

Disease context

Wilms tumor 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Frasier syndrome WAGR syndrome Denys-Drash syndrome

Similar variants

WT1 p.Val373Met Conflicting classifications of pathogenicity ★ same residue
WT1 p.Val373Ala 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
WT1 p.Arg374Ter 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-val373 (accessed [today's date]).

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