Is WT1 p.Ala357= (c.1071C>G) pathogenic?

WT1 p.Ala357= (c.1071C>G) is classified Likely benign in WT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Very rare (popmax 0.00267%, afr); Associated with Frasier syndrome.

What condition is associated with WT1 p.Ala357= (c.1071C>G)?

WT1 p.Ala357= (c.1071C>G) is associated with Frasier syndrome, Wilms tumor 1, WAGR syndrome (ClinVar).

How common is WT1 p.Ala357= (c.1071C>G) in the general population?

WT1 p.Ala357= (c.1071C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Frasier syndrome inherited?

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

WT1 p.Ala357=

c.1071C>G · rs775630812 · VCV2053066

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Frasier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.078	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP -1.5, phastCons 0.97
Overall
CADD	5.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,928 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,614,092 alleles · very rare exomes 2/1,461,884 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,464
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	8.47e-05%	1,180,052

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.Ala357=
Coding: c.1071C>G
MANE Select: NM_024426
dbSNP: rs775630812
Type: single nucleotide variant
Location: chr11:32399990 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 357: a β-strand

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.Ala357Pro Uncertain significance ★★ same residue
WT1 p.Ala357Thr Uncertain significance ★★ same residue
WT1 p.Ala357Val Uncertain significance ★★ same residue
WT1 p.Ala357Asp Uncertain significance ★ same residue
WT1 p.Ala357Ser 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

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-ala357 (accessed [today's date]).

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