SYN2 p.Ser540=
c.1620G>A · rs151063425 · VCV3053612
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.639%, afr)
Conditions
1
SYN2-related disorder
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 8 | GERP 0.35, phastCons 1 |
| Overall | ||
| CADD | 15.41 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.639%
African / African-American · 479/75,008 alleles
Filtering AF
0.591%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.573%
Overall
0.0375%
605/1,613,490 alleles · rare
exomes 316/1,461,264 · genomes 289/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.639% | 157 |
| Admixed American | 0.0901% | 1,110 |
| Remaining individualsnot grpmax-eligible | 0.0784% | 1,275 |
| South Asian | 0.0044% | 22,749 |
| East Asian | 0.00223% | 44,830 |
| European (non-Finnish) | 0.00153% | 65,539 |
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
- SYN2
- Protein
- p.Ser540=
- Coding
- c.1620G>A
- MANE Select
- NM_133625
- dbSNP
- rs151063425
- Type
- single nucleotide variant
- Location
- chr3:12190496 (GRCh38)
- Gene constraint
- LOEUF 0.539 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24
- Residue 540
- the 'disordered' region; the 'e' region
Disease context
SYN2-related disorder
Similar variants
- SYN2 c.1308+1G>A Uncertain significance same condition
- SYN2 p.Ala193Val Benign same condition
- SYN2 p.Ala566= Benign same condition
- SYN2 p.Lys128Arg Benign same condition
- SYN2 p.Thr263= Likely benign same condition
- SYN2 c.1370-4del Likely benign same condition
- SYN2 p.Ala54Val Benign ★★ same type
- SYN2 p.Thr506Ala 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/syn2-p-ser540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown