SETD1A p.Pro1476=
c.4428A>G · rs146489114 · VCV3040808
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0773%, 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 -1.2 | GERP -4.9 |
| Overall | ||
| CADD | 4.897 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0773%
African / African-American · 58/75,046 alleles
Filtering AF
0.0613%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0556%
Overall
0.00378%
61/1,613,904 alleles · ultra-rare
exomes 23/1,461,586 · genomes 38/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0773% | 1,294 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,833 |
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.Pro1476=
- Coding
- c.4428A>G
- MANE Select
- NM_014712
- dbSNP
- rs146489114
- Type
- single nucleotide variant
- Location
- chr16:30980504 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 1476
- the 'interaction with ash2l, rbbp5 and wdr5' region; 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-pro1476 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown