SETD1A p.Ala233=
c.699G>A · rs145879879 · VCV2646421
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.052%, 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 -0.15 | GERP -4.9, phastCons 0.015 |
| Overall | ||
| CADD | 3.387 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.052%
African / African-American · 39/75,008 alleles
Filtering AF
0.039%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0345%
Overall
0.00403%
65/1,614,020 alleles · ultra-rare
exomes 44/1,461,860 · genomes 21/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.052% | 1,923 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,834 |
| European (non-Finnish) | 0.00195% | 51,303 |
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.Ala233=
- Coding
- c.699G>A
- MANE Select
- NM_014712
- dbSNP
- rs145879879
- Type
- single nucleotide variant
- Location
- chr16:30964153 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 233
- a UniProt-annotated variant site (in nedsid); the 'disordered' region
Similar variants
- SETD1A p.Ala233Val Likely benign ★ 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-ala233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown