Is WT1 p.Pro71Thr (c.211C>A) pathogenic?

WT1 p.Pro71Thr (c.211C>A) is classified Uncertain significance in WT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-17). Very rare (popmax 0.00253%, eas); Associated with Denys-Drash syndrome.

What condition is associated with WT1 p.Pro71Thr (c.211C>A)?

WT1 p.Pro71Thr (c.211C>A) is associated with Denys-Drash syndrome, malignant mesothelioma, Frasier syndrome (ClinVar).

How common is WT1 p.Pro71Thr (c.211C>A) in the general population?

WT1 p.Pro71Thr (c.211C>A) is very rare (popmax 0.00253%, eas) (gnomAD).

How is Denys-Drash syndrome inherited?

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

WT1 p.Pro71Thr

c.211C>A · rs1392405207 · VCV965500

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00253%, eas)

Conditions

Denys-Drash syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.051	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.52	GERP -0.67, phastCons 0.011
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic
Overall
CADD	12.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00253% East Asian · 1/39,594 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000394% 6/1,522,930 alleles · very rare exomes 6/1,370,802 · genomes 0/152,128 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00253%	39,594
South Asian	0.00121%	82,878
European (non-Finnish)	0.00035%	285,425

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.Pro71Thr
Coding: c.211C>A
MANE Select: NM_024426
dbSNP: rs1392405207
Type: single nucleotide variant
Location: chr11:32435150 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 71: the 'disordered' region

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: malignant mesothelioma Frasier syndrome Wilms tumor 1 WAGR syndrome nephrotic syndrome, type 4 Meacham syndrome

For Denys-Drash syndrome (Orphanet):

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

Similar variants

WT1 p.Pro71Ser 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-pro71thr (accessed [today's date]).

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