Is WT1 p.Ala66fs (c.196del) pathogenic?

WT1 p.Ala66fs (c.196del) is classified Uncertain significance in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-04). No allele count reported in gnomAD v4.1 (AN 1,520,520); Associated with Frasier syndrome.

What condition is associated with WT1 p.Ala66fs (c.196del)?

WT1 p.Ala66fs (c.196del) is associated with Frasier syndrome, Wilms tumor 1, WAGR syndrome (ClinVar).

How common is WT1 p.Ala66fs (c.196del) in the general population?

WT1 p.Ala66fs (c.196del) is no allele count reported in gnomAD v4.1 (AN 1,520,520) (gnomAD).

How is Frasier syndrome inherited?

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

WT1 p.Ala66fs

c.196del · rs2494486834 · VCV2951591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,520,520)

Conditions

Frasier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -2.8, phastCons 0.001

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,520,520). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: WT1
Protein: p.Ala66fs
Coding: c.196del
MANE Select: NM_024426
dbSNP: rs2494486834
Type: Deletion
Location: chr11:32435165 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 66: the 'disordered' region

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.Ala66Glu Uncertain significance ★★ same residue
WT1 p.Ala66= Likely benign ★★ same residue
WT1 p.Pro137fs Pathogenic/Likely pathogenic ★★ same condition
WT1 c.1354+4_1354+11del Likely pathogenic ★ same condition
WT1 c.882_887+3del Pathogenic ★ same condition
WT1 p.Arg476fs Likely pathogenic ★ same condition
WT1 p.Arg500fs Likely pathogenic ★ same condition
WT1 p.Gln457_Cys458insTer 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-ala66fs (accessed [today's date]).

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