Is WT1 p.Ter523= (c.1568G>A) pathogenic?

WT1 p.Ter523= (c.1568G>A) is classified Conflicting classifications of pathogenicity in WT1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2025-11-23). Rare (popmax 0.132%, mid); Associated with kidney disorder.

What condition is associated with WT1 p.Ter523= (c.1568G>A)?

WT1 p.Ter523= (c.1568G>A) is associated with kidney disorder, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Ter523= (c.1568G>A) in the general population?

WT1 p.Ter523= (c.1568G>A) is rare (popmax 0.132%, mid) (gnomAD).

WT1 p.Ter523=

c.1568G>A · rs148856160 · VCV515922

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Conditions

kidney disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.42, phastCons 1
Overall
CADD	11.25	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,060 alleles

Filtering AF 0.0657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.00229% 37/1,614,222 alleles · rare exomes 34/1,461,860 · genomes 3/152,362 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
Remaining individualsnot grpmax-eligible	0.0064%	15,627
South Asian	0.0022%	45,541
European (non-Finnish)	0.00186%	53,638
Admixed American	0.00167%	60,034

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.Ter523=
Coding: c.1568G>A
MANE Select: NM_024426
dbSNP: rs148856160
Type: single nucleotide variant
Location: chr11:32389059 (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

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Frasier syndrome Wilms tumor 1 WAGR syndrome Denys-Drash syndrome nephrotic syndrome, type 4 Meacham syndrome

Similar variants

WT1 p.Ter523Trp 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
WT1 p.Arg435Ter 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-ter523 (accessed [today's date]).

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