--- title: "WT1 H450Y (c.1348C>T, rs28942089) | Dante Labs" description: "ClinVar classifies WT1 H450Y as Pathogenic/likely pathogenic (criteria provided, multiple submitters, no conflicts). Where it sits in the genome, its predicted effect, and the Genome Test reports that look at it." url: "https://dantelabs.com/genes/wt1/variants/h450y" --- 1. [Genes](https://dantelabs.com/genes) 2. [WT1](https://dantelabs.com/genes/wt1) 3. WT1 H450Y Variant # WT1 H450Y NM_024426.6(WT1):c.1348C>T (p.His450Tyr) Also known as - H377Y - p.His450Tyr - p.H450Y - rs28942089 * ClinVar classification Pathogenic/likely pathogenic * Review status 2 stars out of 4 criteria provided, multiple submitters, no conflicts * Last evaluated 9 October 2022 Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.19-9814e911 Facts last changed 19 October 2026 ## Summary H450Y is a missense variant in WT1: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as pathogenic or likely pathogenic for Denys-Drash syndrome (criteria provided, multiple submitters, no conflicts). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | --------------------------------------------------------------------------------------------------------------------- | ---------------------------- | --------------------------------------------------------------------- | ------------- | -------------- | | Denys-Drash syndrome[ClinVar VCV000003495 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/3495/) | Pathogenic/likely pathogenic | 2 stars out of 4 criteria provided, multiple submitters, no conflicts | 2 submissions | 9 October 2022 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria H450Y meets, from its predicted effect in WT1, gnomAD and ClinVar. | Criterion | Strength | Points | Rests on | | ----------------------------------------------- | ---------- | ----------- | -------------------------------------------------------------------------------------------- | | PM2 Absent or very rare in population databases | Supporting | +1 | Not seen in gnomAD exomes, gnomAD genomes | | PP5 A reputable source reports it as pathogenic | Supporting | Not counted | ClinVar: Pathogenic/likely pathogenic (criteria provided, multiple submitters, no conflicts) | On these criteria alone: +1 point, uncertain significance. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## Population frequency How often H450Y is seen among the people whose exomes and genomes gnomAD 4.1 brings together. | Dataset | Allele frequency | Allele count | Homozygotes | Commonest in | | -------------- | ---------------- | ------------ | ----------- | ------------ | | gnomAD exomes | Not seen | 0 of 0 | 0 | | | gnomAD genomes | Not seen | 0 of 0 | 0 | | Figures from gnomAD 4.1, as gnomAD publishes them. Groups are genetic ancestry groups as gnomAD infers them. They describe the variant in gnomAD's populations, not anyone's result. [H450Y in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/11-32392672-G-A?dataset=gnomad_r4) ## Molecular details | Gene | [WT1](https://dantelabs.com/genes/wt1) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_024426.6 MANE Select | | Coding DNA change (HGVS c.) | c.1348C>T | | Protein change (HGVS p.) | p.His450Tyr p.H450Y | | Predicted consequence | Missense [missense_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001583) | | Predicted impact | Moderate | | Position (GRCh38) | chr11:32392672 G>A | | Position (GRCh37) | chr11:32414218 G>A | | dbSNP ID | [rs28942089 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs28942089) | | ClinVar Variation ID | [VCV000003495 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/3495/) | | ClinVar Allele ID | 18534 | | ClinGen Allele Registry ID | [CA016298 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA016298) | | ClinVar name | NM_024426.6(WT1):c.1348C>T (p.His450Tyr) | | Other names | H377Y | ## WT1 H450Y in other databases - [ClinVar VCV000003495 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/3495/) - [dbSNP rs28942089 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs28942089) - [ClinGen Allele Registry CA016298 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA016298) - [gnomAD 11-32392672-G-A (opens in a new tab)](https://gnomad.broadinstitute.org/variant/11-32392672-G-A?dataset=gnomad_r4) - [Ensembl rs28942089 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs28942089) ## Reports that look at this variant (1) These Genome Test condition reports include H450Y among the variants they look at. | Report | Conditions | Inheritance | | ------------------------------------------------------------------------------------------------------------------------------------ | ------------------------------------ | ----------- | | [46,XY Differences of Sex Development and Gonadal Dysgenesis](https://dantelabs.com/conditions/46-xy-differences-of-sex-development) | 46,XY differences of sex development | | ## Other variants in WT1 - [c.965+1G>A Likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/c-965plus1g-a) - [c.1447+4C>T1432+4C>T Pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/c-1447plus4c-t) - [c.1447+5G>A1432+5G>A Pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/c-1447plus5g-a) - [c.1448-1G>A Likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/c-1448-1g-a) - [G152Afs\*11 Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/g152afs11) - [H446Q Pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/h446q) - [P137Rfs\*26 Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/p137rfs26) - [Q462X Likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/q462x) - [R374X Pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/r374x) - [R385Gfs\*5 Pathogenic/likely pathogenic 2 stars out of 4](https://dantelabs.com/genes/wt1/variants/r385gfs5) [All WT1 variants](https://dantelabs.com/genes/wt1/variants) ## Limitations This page describes publicly available information about a genetic variant. It is not a diagnosis, and it says nothing about whether you or anyone else carries this variant. Classifications come from ClinVar and change as new evidence is reviewed. A classification here may differ from the one in ClinVar today, or from the one a laboratory reports. Whole genome sequencing with short reads can miss or miscall some variants, particularly in repeated or highly similar stretches of DNA and in large insertions, deletions or rearrangements. If you have questions about a variant in your own results or in your family, talk to a genetic counsellor or your doctor. ## Sources & credits - Classifications from ClinVar (release 2026-10-12), National Center for Biotechnology Information. - Condition terms from the Mondo Disease Ontology (release 2026-10-06), used under CC BY 4.0. - Gene symbols and names from the HUGO Gene Nomenclature Committee (release 2026-10-16). - Allele identifiers from the ClinGen Allele Registry (release 2026-10-19-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-19). - Difficult regions from the Genome in a Bottle Consortium (release v3.6). - Transcripts from MANE (release v1.5), NCBI and EMBL-EBI. - Predicted consequences from mehari (release 0.11.0), with transcript models from cdot. - Built from Dante Labs data release 2026.10.19-9814e911 of 19 October 2026. ## Cite this page APA > Dante Labs. (19 October 2026). WT1 H450Y (c.1348C>T, rs28942089) (Version 2026.10.19-9814e911). Retrieved 21 October 2026, from https\://dantelabs.com/genes/wt1/variants/h450y Vancouver > Dante Labs. WT1 H450Y (c.1348C>T, rs28942089) \[Internet]. Version 2026.10.19-9814e911. 19 October 2026 \[cited 21 October 2026]. Available from: https\://dantelabs.com/genes/wt1/variants/h450y Download citation [RIS](https://dantelabs.com/genes/wt1/variants/h450y/cite.ris) [BibTeX](https://dantelabs.com/genes/wt1/variants/h450y/cite.bib) [CSL-JSON](https://dantelabs.com/genes/wt1/variants/h450y/cite.json) ## Read your whole genome From $449 Free shipping · Results in 6–8 weeks [Explore the Genome Test](https://dantelabs.com/whole-genome-sequencing)