Is WT1 p.Gln358= (c.1074A>G) pathogenic?

WT1 p.Gln358= (c.1074A>G) is classified Benign in WT1 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-03). Common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with WT1 p.Gln358= (c.1074A>G)?

WT1 p.Gln358= (c.1074A>G) is associated with Inborn genetic diseases, kidney disorder, Frasier syndrome (ClinVar).

WT1 p.Gln358=

Q: How common is WT1 p.Gln358= (c.1074A>G) in the general population?

WT1 p.Gln358= (c.1074A>G) is common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1074A>G · rs2234590 · VCV261708

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Common

common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.14	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -2.9, phastCons 1
Overall
CADD	9.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.9% African / African-American · 11,196/75,002 alleles

Filtering AF 14.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 0.828% 13,359/1,614,154 alleles · common exomes 6,749/1,461,888 · genomes 6,610/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.9%	7
Admixed American	1.21%	82
Remaining individualsnot grpmax-eligible	1.1%	91
Middle Eastern	1.04%	96
Ashkenazi Jewishnot grpmax-eligible	0.378%	264
South Asian	0.0582%	1,718
European (non-Finnish)	0.0439%	2,278
Finnishnot grpmax-eligible	0.00156%	64,046

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.Gln358=
Coding: c.1074A>G
MANE Select: NM_024426
dbSNP: rs2234590
Type: single nucleotide variant
Location: chr11:32399987 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 52.09 · 31 PDB
Residue 358: a β-strand

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: kidney disorder Frasier syndrome Wilms tumor 1 WAGR syndrome Denys-Drash syndrome nephrotic syndrome, type 4 Meacham syndrome

Similar variants

WT1 p.Gln358Arg Uncertain significance ★★ same residue
WT1 p.Gln358Glu 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
WT1 p.Arg374Ter 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-gln358 (accessed [today's date]).

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