SETD2 p.Thr444=
c.1332G>A · VCV3667251
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00685%, afr)
Conditions
1
Luscan-Lumish syndrome
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 0.12 | GERP -4.6, phastCons 0.97 |
| Overall | ||
| CADD | 9.153 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00685%
African / African-American · 5/72,982 alleles
Filtering AF
0.0026%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00165%
Overall
0.00148%
23/1,551,606 alleles · very rare
exomes 18/1,399,536 · genomes 5/152,070 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00685% | 14,596 |
| East Asian | 0.00244% | 40,938 |
| South Asian | 0.00238% | 42,054 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,108 |
| European (non-Finnish) | 0.00122% | 81,929 |
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.Thr444=
- Coding
- c.1332G>A
- MANE Select
- NM_014159
- Type
- single nucleotide variant
- Location
- chr3:47123304 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.81 · 43 PDB
- Residue 444
- a UniProt-annotated variant site (in aml; uncertain significance; somatic mutation); the 'disordered' region
Similar variants
- SETD2 p.Thr444Lys Uncertain significance ★ ⚠ same residue
- SETD2 p.Thr444Met Likely benign ★ same residue
- SETD2 p.Thr444Ala Likely benign ★ same residue
- SETD2 p.Arg1598Ter Pathogenic/Likely pathogenic ★★ same condition
- SETD2 p.Arg1740Gln Pathogenic ★★ ⚠ same condition
- SETD2 p.Arg1740Trp Pathogenic/Likely pathogenic ★★ same condition
- SETD2 p.Ala1121Thr Uncertain significance ★★ ⚠ same condition
- SETD2 p.Ala679Val Uncertain significance ★★ ⚠ 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/setd2-p-thr444 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown