INSYN2B p.Ser474=
c.1422T>C · rs1449991385 · VCV3109998
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0368%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not looked up on this page · why |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.96 | GERP -0.55, phastCons 0.99 |
| Overall | ||
| CADD | 10.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0368%
East Asian · 15/40,762 alleles
Filtering AF
0.0226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0183%
Overall
0.00118%
18/1,526,132 alleles · ultra-rare
exomes 16/1,374,050 · genomes 2/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0368% | 2,717 |
| African / African-American | 0.00278% | 36,000 |
| European (non-Finnish) | 8.81e-05% | 1,135,362 |
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
- INSYN2B
- Protein
- p.Ser474=
- Coding
- c.1422T>C
- MANE Select
- NM_001129891
- dbSNP
- rs1449991385
- Type
- single nucleotide variant
- Location
- chr5:169864459 (GRCh38)
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/insyn2b-p-ser474 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown