SETD1A p.Ala756=
c.2268C>T · rs370636455 · VCV709311
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.111%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.59 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.38 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -5.1 |
| Overall | ||
| CADD | 18.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.111%
Admixed American · 66/59,490 alleles
Filtering AF
0.0894%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0816%
Overall
0.0192%
308/1,605,456 alleles · rare
exomes 266/1,453,286 · genomes 42/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.111% | 901 |
| Middle Eastern | 0.0991% | 1,009 |
| Remaining individualsnot grpmax-eligible | 0.0484% | 2,068 |
| European (non-Finnish) | 0.0167% | 5,997 |
| African / African-American | 0.0107% | 9,349 |
| East Asian | 0.00223% | 44,766 |
| Finnishnot grpmax-eligible | 0.0016% | 62,580 |
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.Ala756=
- Coding
- c.2268C>T
- MANE Select
- NM_014712
- dbSNP
- rs370636455
- Type
- single nucleotide variant
- Location
- chr16:30966149 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 756
- a UniProt-annotated variant site (in nedsid)
Similar variants
- SETD1A p.Ala756Thr Likely benign ★ same residue
- 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
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-ala756 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown