SETD1A p.Ala701=
c.2103C>T · rs373029609 · VCV2646434
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0169%, 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 -0.44 | GERP -4.4, phastCons 0.073 |
| Overall | ||
| CADD | 4.594 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0169%
Middle Eastern · 1/5,924 alleles
Filtering AF
0.00349%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0024%
Overall
0.00214%
34/1,585,864 alleles · ultra-rare
exomes 25/1,433,676 · genomes 9/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0169% | 5,924 |
| African / African-American | 0.00807% | 12,392 |
| Remaining individualsnot grpmax-eligible | 0.00327% | 30,582 |
| East Asian | 0.00224% | 44,590 |
| European (non-Finnish) | 0.00197% | 50,671 |
| South Asian | 0.00115% | 86,734 |
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.Ala701=
- Coding
- c.2103C>T
- MANE Select
- NM_014712
- dbSNP
- rs373029609
- Type
- single nucleotide variant
- Location
- chr16:30965984 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 701
- 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-ala701 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown