SIN3B p.Ile647=
c.1941C>T · rs151138680 · VCV2649521
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 1.7 | GERP -4.6, phastCons 1 |
| Overall | ||
| CADD | 11.43 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00939%
Overall
0.00954%
154/1,613,586 alleles · ultra-rare
exomes 145/1,461,234 · genomes 9/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| European (non-Finnish) | 0.0116% | 8,613 |
| South Asian | 0.00769% | 13,012 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| African / African-American | 0.00266% | 37,534 |
| Admixed American | 0.00167% | 60,038 |
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.Ile647=
- Coding
- c.1941C>T
- MANE Select
- NM_001297595
- dbSNP
- rs151138680
- Type
- single nucleotide variant
- Location
- chr19:16869594 (GRCh38)
- Gene constraint
- LOEUF 0.245 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.07 · 4 PDB
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-ile647 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown