SIN3B p.Ser378=
c.1134C>T · VCV3911379
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.187%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -4.6 |
| Overall | ||
| CADD | 9.528 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.187%
African / African-American · 140/75,002 alleles
Filtering AF
0.161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.152%
Overall
0.0172%
277/1,614,120 alleles · rare
exomes 192/1,461,880 · genomes 85/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.187% | 536 |
| Middle Eastern | 0.148% | 674 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0642% | 1,558 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,718 |
| South Asian | 0.0143% | 7,006 |
| Admixed American | 0.0133% | 7,503 |
| European (non-Finnish) | 0.00551% | 18,154 |
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
- SIN3B
- Protein
- p.Ser378=
- Coding
- c.1134C>T
- MANE Select
- NM_001297595
- Type
- single nucleotide variant
- Location
- chr19:16862427 (GRCh38)
- Gene constraint
- LOEUF 0.245 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.07 · 4 PDB
- Residue 378
- the 'interaction with ncor1' region
Similar variants
- SIN3B p.Ala534Thr Uncertain significance ★★ same type
- SIN3B p.Glu258Asp Uncertain significance ★★ ⚠ same type
- SIN3B p.His91Tyr Uncertain significance ★★ ⚠ same type
- SIN3B p.Pro281Ala Uncertain significance ★★ ⚠ same type
- SIN3B p.Val160Met Uncertain significance ★★ ⚠ same type
- SIN3B p.Val873Ile Uncertain significance ★★ ⚠ same type
- SIN3B c.1266+354G>A Benign ★★ same type
- SIN3B c.2954+6A>G Benign ★★ 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/sin3b-p-ser378 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown