SETD1A p.Leu732=
c.2196A>G · rs201876288 · VCV2646436
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0292%, eas)
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 1 | GERP -4.7, phastCons 1 |
| Overall | ||
| CADD | 6.273 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0292%
East Asian · 13/44,550 alleles
Filtering AF
0.0172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00176%
28/1,588,218 alleles · ultra-rare
exomes 27/1,436,104 · genomes 1/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0292% | 3,427 |
| South Asian | 0.00686% | 14,571 |
| Admixed American | 0.00173% | 57,882 |
| African / African-American | 0.00134% | 74,500 |
| European (non-Finnish) | 0.0006% | 166,572 |
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
- SETD1A
- Protein
- p.Leu732=
- Coding
- c.2196A>G
- MANE Select
- NM_014712
- dbSNP
- rs201876288
- Type
- single nucleotide variant
- Location
- chr16:30966077 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 732
- a UniProt-annotated variant site (in nedsid)
Similar variants
- SETD1A c.518-2A>G Pathogenic ★★ same type
- SETD1A p.Arg1571Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Arg176Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Arg668Ter Pathogenic ★★ same type
- SETD1A p.Arg913Cys Likely pathogenic ★★ ⚠ same type
- SETD1A p.Arg990Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1A p.Tyr646Ter Pathogenic ★★ same type
- SETD1A c.4692+3G>A 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/setd1a-p-leu732 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown