SETD1A p.Ser295del
c.881CCT[1] · VCV4534351
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0692%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.87 | GERP -3.9, phastCons 0.015 |
| Overall | ||
| CADD | 17.88 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0692%
East Asian · 31/44,800 alleles
Filtering AF
0.0501%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0435%
Overall
0.00223%
36/1,611,994 alleles · ultra-rare
exomes 30/1,460,446 · genomes 6/151,548 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0692% | 1,445 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish) | 0.000339% | 294,812 |
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.Ser295del
- Coding
- c.881CCT[1]
- MANE Select
- NM_014712
- Type
- Microsatellite
- Location
- chr16:30964623 (GRCh38)
- Gene constraint
- LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.20 · 4 PDB
- Residue 295
- a UniProt-annotated variant site (in nedsid); the 'disordered' region
Similar variants
- SETD1A p.Glu1368fs Uncertain significance ★★ same type
- SETD1A p.1361GEEE[2] Likely benign ★★ same type
- SETD1A p.Ser1058del Likely benign ★★ same type
- SETD1A p.Ser1383_Asp1384insSer Likely benign ★★ same type
- SETD1A p.Asp73fs Pathogenic ★ same type
- SETD1A p.Glu1002fs Likely pathogenic ★ same type
- SETD1A p.Ser411fs Pathogenic ★ same type
- SETD1A p.Val994fs 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/setd1a-p-ser295del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown