Is WT1 p.Ala380= (c.1140C>A) pathogenic?

WT1 p.Ala380= (c.1140C>A) is classified Likely benign in WT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with WT1 p.Ala380= (c.1140C>A)?

WT1 p.Ala380= (c.1140C>A) is associated with Inborn genetic diseases, Frasier syndrome, Wilms tumor 1 (ClinVar).

How common is WT1 p.Ala380= (c.1140C>A) in the general population?

WT1 p.Ala380= (c.1140C>A) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

WT1 p.Ala380=

c.1140C>A · rs147126640 · VCV543145

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.091	GERP -4, phastCons 0.14
Overall
CADD	6.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,918 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.000991% 16/1,613,974 alleles · ultra-rare exomes 6/1,461,812 · genomes 10/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,351
Admixed American	0.00333%	29,998

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.Ala380=
Coding: c.1140C>A
MANE Select: NM_024426
dbSNP: rs147126640
Type: single nucleotide variant
Location: chr11:32396381 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 380: the 'important for interaction with target dna' region

Full WT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

WT1 p.Ala380Asp Uncertain significance ★★ same residue
WT1 p.Ala380Thr Uncertain significance ★ same residue
WT1 p.Ala380Val 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

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-ala380 (accessed [today's date]).

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