Is WT1 p.Arg61= (c.181C>A) pathogenic?

WT1 p.Arg61= (c.181C>A) is classified Benign/Likely benign in WT1 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.59%, amr); Associated with Frasier syndrome.

What condition is associated with WT1 p.Arg61= (c.181C>A)?

WT1 p.Arg61= (c.181C>A) is associated with Frasier syndrome, Wilms tumor 1, WAGR syndrome (ClinVar).

How common is WT1 p.Arg61= (c.181C>A) in the general population?

WT1 p.Arg61= (c.181C>A) is low-frequency (popmax 3.59%, amr) (gnomAD).

How is Frasier syndrome inherited?

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

WT1 p.Arg61=

c.181C>A · rs2234581 · VCV241476

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.59%, amr)

Conditions

Frasier syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 10	GERP 0.47, phastCons 1
Overall
CADD	12.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.59% Admixed American · 1,792/49,888 alleles

Filtering AF 3.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.4%

Overall 0.136% 2,066/1,521,766 alleles · low-frequency exomes 1,661/1,369,642 · genomes 405/152,124 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.59%	28
Finnishnot grpmax-eligible	0.15%	665
Remaining individualsnot grpmax-eligible	0.113%	882
African / African-American	0.0724%	1,381
European (non-Finnish)	0.00737%	13,573
East Asian	0.005%	19,987
Ashkenazi Jewishnot grpmax-eligible	0.00357%	27,998
South Asian	0.00241%	41,500

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.Arg61=
Coding: c.181C>A
MANE Select: NM_024426
dbSNP: rs2234581
Type: single nucleotide variant
Location: chr11:32435180 (GRCh38)

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 nephrotic syndrome, type 4 Meacham syndrome focal segmental glomerulosclerosis

For Frasier syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

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-arg61 (accessed [today's date]).

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