Is WT1 p.His340= (c.1020C>T) pathogenic?

WT1 p.His340= (c.1020C>T) is classified Conflicting classifications of pathogenicity in WT1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-03). Ultra-rare (popmax 0.016%, afr); Associated with nephrotic syndrome, type 4.

What condition is associated with WT1 p.His340= (c.1020C>T)?

WT1 p.His340= (c.1020C>T) is associated with nephrotic syndrome, type 4, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.His340= (c.1020C>T) in the general population?

WT1 p.His340= (c.1020C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

WT1 p.His340=

c.1020C>T · rs375114529 · VCV877125

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Conditions

nephrotic syndrome, type 4

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 -8.1	GERP -5.1
Overall
CADD	2.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,942 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.000805% 13/1,614,098 alleles · ultra-rare exomes 5/1,461,862 · genomes 8/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,245
Admixed American	0.00167%	60,008

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.His340=
Coding: c.1020C>T
MANE Select: NM_024426
dbSNP: rs375114529
Type: single nucleotide variant
Location: chr11:32400041 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 340: an α-helix

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

Disease context

nephrotic syndrome, type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Frasier syndrome Wilms tumor 1 WAGR syndrome Denys-Drash syndrome Meacham syndrome

Similar variants

WT1 p.His340_Ser341delinsGlnArg Uncertain significance ★ same residue
WT1 p.His340Tyr 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-his340 (accessed [today's date]).

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