Is WT1 p.Pro271Gln (c.812C>A) pathogenic?

WT1 p.Pro271Gln (c.812C>A) is classified Uncertain significance in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Absent from gnomAD v4.1; Associated with Frasier syndrome.

What condition is associated with WT1 p.Pro271Gln (c.812C>A)?

WT1 p.Pro271Gln (c.812C>A) is associated with Frasier syndrome, Wilms tumor 1, WAGR syndrome (ClinVar).

How common is WT1 p.Pro271Gln (c.812C>A) in the general population?

WT1 p.Pro271Gln (c.812C>A) is absent from gnomAD v4.1 (gnomAD).

How is Frasier syndrome inherited?

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

WT1 p.Pro271Gln

c.812C>A · rs1226711237 · VCV2946545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Frasier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.692	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 39 kb · p 0.077 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: WT1
Protein: p.Pro271Gln
Coding: c.812C>A
MANE Select: NM_024426
dbSNP: rs1226711237
Type: single nucleotide variant
Location: chr11:32428031 (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

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

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

For Frasier syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

WT1 p.Pro271fs Pathogenic ★ same residue
WT1 p.Pro271Arg Uncertain significance ★ same residue
WT1 p.Pro271= Likely benign ★ 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-pro271gln (accessed [today's date]).

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