SYN2 p.Ala566=
c.1698A>G · rs310764 · VCV3059730
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
SYN2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.082 | GERP -5, phastCons 0.074 |
| Overall | ||
| CADD | 5.225 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
East Asian · 44,804/44,816 alleles
Filtering AF
99.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 98.9%
Overall
91.4%
1,474,462/1,613,242 alleles · common
exomes 1,331,965/1,460,936 · genomes 142,497/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| African / African-American | 97.6% | 1 |
| Middle Eastern | 96.9% | 1 |
| Admixed American | 95.7% | 1 |
| South Asian | 95.3% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 94.6% | 1 |
| Finnishnot grpmax-eligible | 93.3% | 1 |
| Amishnot grpmax-eligible | 93% | 1 |
| Remaining individualsnot grpmax-eligible | 92.7% | 1 |
| European (non-Finnish) | 89.9% | 1 |
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.Ala566=
- Coding
- c.1698A>G
- MANE Select
- NM_133625
- dbSNP
- rs310764
- Type
- single nucleotide variant
- Location
- chr3:12190574 (GRCh38)
- Gene constraint
- LOEUF 0.539 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 75.24
- Residue 566
- 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.Lys128Arg Benign same condition
- SYN2 p.Ser540= 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-ala566 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown