Is WT1 p.Ser386= (c.1158G>T) pathogenic?

WT1 p.Ser386= (c.1158G>T) is classified Likely benign in WT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with WT1 p.Ser386= (c.1158G>T)?

WT1 p.Ser386= (c.1158G>T) is associated with Inborn genetic diseases (ClinVar).

How common is WT1 p.Ser386= (c.1158G>T) in the general population?

WT1 p.Ser386= (c.1158G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

WT1 p.Ser386=

c.1158G>T · VCV3817477

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.178	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -5.4
Overall
CADD	0.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.2e-05% 1/1,614,088 alleles · very rare exomes 1/1,461,862 · genomes 0/152,226 · joint denominator

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.Ser386=
Coding: c.1158G>T
MANE Select: NM_024426
Type: single nucleotide variant
Location: chr11:32396363 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 386: a turn

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

Similar variants

WT1 p.Ser386Ter Pathogenic ★ same residue
WT1 p.Ser386Leu Uncertain significance ★★ same residue
WT1 c.1016+4A>C Uncertain significance ★★ same condition
WT1 c.1113+5G>A Uncertain significance ★★ same condition
WT1 c.1113+5G>C Uncertain significance ★★ same condition
WT1 c.1448-3C>T Uncertain significance ★★ same condition
WT1 c.888-1G>A Uncertain significance ★★ same condition
WT1 c.965+5G>A Uncertain significance ★★ 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-ser386 (accessed [today's date]).

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