SIN3A p.Ser590=
c.1770G>A · rs373830836 · VCV1904004
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0066%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.46 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.31 | GERP -4, phastCons 0.052 |
| Overall | ||
| CADD | 9.414 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0066%
South Asian · 6/90,906 alleles
Filtering AF
0.00287%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.000746%
12/1,609,262 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0066% | 15,151 |
| African / African-American | 0.00401% | 24,912 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,145 |
| European (non-Finnish) | 8.5e-05% | 1,176,060 |
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
- SIN3A
- Protein
- p.Ser590=
- Coding
- c.1770G>A
- MANE Select
- NM_001145358
- dbSNP
- rs373830836
- Type
- single nucleotide variant
- Location
- chr15:75400124 (GRCh38)
- Gene constraint
- LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.67
- Residue 590
- the 'interaction with ncor1' region; the 'interaction with suds3 and sap130' region
Similar variants
- SIN3A p.Arg1140Ter Pathogenic ★★ same type
- SIN3A p.Arg471Ter Pathogenic ★★ same type
- SIN3A p.Arg537Ter Pathogenic ★★ same type
- SIN3A p.Arg553Ter Pathogenic/Likely pathogenic ★★ same type
- SIN3A p.Arg559Ter Pathogenic/Likely pathogenic ★★ same type
- SIN3A p.Arg718Ter Pathogenic/Likely pathogenic ★★ same type
- SIN3A p.Arg897Ter Pathogenic ★★ same type
- SIN3A p.Arg935Ter 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/sin3a-p-ser590 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown