SETD1A p.Ser974=
c.2922G>A · rs76415929 · VCV774922
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.52%, afr)
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 -4.8 | GERP -5 |
| Overall | ||
| CADD | 1.162 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.52%
African / African-American · 2,641/74,966 alleles
Filtering AF
3.41%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.37%
Overall
0.361%
5,811/1,610,256 alleles · low-frequency
exomes 4,074/1,457,938 · genomes 1,737/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.52% | 28 |
| Remaining individualsnot grpmax-eligible | 0.343% | 291 |
| Admixed American | 0.308% | 324 |
| South Asian | 0.216% | 462 |
| European (non-Finnish) | 0.215% | 466 |
| Middle Eastern | 0.099% | 1,010 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0915% | 1,093 |
| Finnishnot grpmax-eligible | 0.022% | 4,555 |
| East Asian | 0.00447% | 22,348 |
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.Ser974=
- Coding
- c.2922G>A
- MANE Select
- NM_014712
- dbSNP
- rs76415929
- Type
- single nucleotide variant
- Location
- chr16:30969456 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 974
- the 'disordered' region; 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-ser974 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown