SETD1A p.Leu690=
c.2070C>T · VCV3388391
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.381%, mid)
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 0.016 | GERP -3.5, phastCons 0.85 |
| Overall | ||
| CADD | 5.117 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.381%
Middle Eastern · 23/6,030 alleles
Filtering AF
0.261%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.221%
Overall
0.0175%
281/1,606,708 alleles · rare
exomes 252/1,454,512 · genomes 29/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.381% | 262 |
| Remaining individualsnot grpmax-eligible | 0.0901% | 1,110 |
| Admixed American | 0.0491% | 2,037 |
| European (non-Finnish) | 0.0143% | 7,002 |
| African / African-American | 0.00401% | 24,947 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00345% | 29,016 |
| South Asian | 0.00111% | 89,966 |
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.Leu690=
- Coding
- c.2070C>T
- MANE Select
- NM_014712
- Type
- single nucleotide variant
- Location
- chr16:30965951 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 690
- 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-leu690 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown