SETD1A p.Pro729=
c.2187G>A · VCV4929477
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0491%, amr)
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 -0.87 | GERP -3.5 |
| Overall | ||
| CADD | 9.584 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0491%
Admixed American · 28/56,998 alleles
Filtering AF
0.0348%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0301%
Overall
0.00727%
115/1,581,544 alleles · ultra-rare
exomes 98/1,429,384 · genomes 17/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0491% | 2,036 |
| East Asian | 0.0135% | 7,423 |
| European (non-Finnish) | 0.00662% | 15,099 |
| Remaining individualsnot grpmax-eligible | 0.00328% | 30,515 |
| African / African-American | 0.00269% | 37,135 |
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.Pro729=
- Coding
- c.2187G>A
- MANE Select
- NM_014712
- Type
- single nucleotide variant
- Location
- chr16:30966068 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 729
- a UniProt-annotated variant site (in nedsid)
Similar variants
- SETD1A p.Pro729Ala 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-pro729 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown