SETD1A p.Pro1097=
c.3291G>A · VCV4929495
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 -0.14 | GERP -5.3, phastCons 0.004 |
| Overall | ||
| CADD | 4.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,934 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.00124%
20/1,610,498 alleles · very rare
exomes 18/1,458,232 · genomes 2/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,987 |
| Admixed American | 0.00167% | 59,804 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,286 |
| South Asian | 0.0011% | 90,880 |
| European (non-Finnish) | 0.00102% | 98,125 |
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.Pro1097=
- Coding
- c.3291G>A
- MANE Select
- NM_014712
- Type
- single nucleotide variant
- Location
- chr16:30971652 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 1097
- the 'disordered' region; a UniProt-annotated variant site (in nedsid)
Similar variants
- SETD1A p.Pro1097Leu Uncertain significance ★ ⚠ 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-pro1097 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown