SETD2 p.Leu363=
c.1087C>T · VCV3772198
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00238%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 5.047 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00238%
South Asian · 2/84,054 alleles
Filtering AF
0.000395%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000148%
Overall
0.000129%
2/1,550,438 alleles · very rare
exomes 2/1,398,168 · genomes 0/152,270 · 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
- SETD2
- Protein
- p.Leu363=
- Coding
- c.1087C>T
- MANE Select
- NM_014159
- Type
- single nucleotide variant
- Location
- chr3:47123549 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 363
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); the 'disordered' region
Similar variants
- SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same type
- SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same type
- SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same type
- SETD2 p.Arg441Ter Likely pathogenic ★★ same type
- SETD2 p.Glu1718Lys Likely pathogenic ★★ ⚠ same type
- SETD2 c.4715+5G>A Uncertain significance ★★ same type
- SETD2 p.Ala1121Thr Uncertain significance ★★ ⚠ same type
- SETD2 p.Ala679Val Uncertain significance ★★ ⚠ same type
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/setd2-p-leu363 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown