SETD2 p.Leu1444=
c.4332G>A · rs2107740070 · VCV2653746
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.51 | GERP -2.6 |
| Overall | ||
| CADD | 1.938 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,950 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,613,984 alleles · very rare
exomes 3/1,461,674 · genomes 0/152,310 · 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.Leu1444=
- Coding
- c.4332G>A
- MANE Select
- NM_014159
- dbSNP
- rs2107740070
- Type
- single nucleotide variant
- Location
- chr3:47120304 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 1444
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); a UniProt-annotated variant site (in all; uncertain significance; somatic mutation); the 'interaction with tuba1a' 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-leu1444 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown