SETD1B p.Ala1216=
c.3648G>A · VCV4918989
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0171%, eas)
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 -2.8 | GERP -2.6 |
| Overall | ||
| CADD | 0.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0171%
East Asian · 7/40,938 alleles
Filtering AF
0.00798%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00564%
Overall
0.00148%
23/1,551,676 alleles · ultra-rare
exomes 21/1,399,462 · genomes 2/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0171% | 5,848 |
| African / African-American | 0.00137% | 73,058 |
| European (non-Finnish) | 0.00122% | 81,932 |
| South Asian | 0.00119% | 84,066 |
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
- SETD1B
- Protein
- p.Ala1216=
- Coding
- c.3648G>A
- MANE Select
- NM_001353345
- Type
- single nucleotide variant
- Location
- chr12:121819633 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 46.43 · 4 PDB
- Residue 1216
- a UniProt-annotated variant site (in iddseld); the 'disordered' region
Similar variants
- SETD1B p.Ala1216Val Uncertain significance ★ ⚠ same residue
- SETD1B p.Arg1329Ter Pathogenic ★★ same type
- SETD1B p.Arg1703Ter Pathogenic/Likely pathogenic ★★ same type
- SETD1B p.Arg1748Cys Pathogenic/Likely pathogenic ★★ same type
- SETD1B p.Arg1792Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- SETD1B p.Arg1825Trp Likely pathogenic ★★ same type
- SETD1B p.Arg1902Cys Pathogenic/Likely pathogenic ★★ same type
- SETD1B p.Gln780Ter Pathogenic/Likely 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/setd1b-p-ala1216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown