SNAP25 p.Ser25=
c.75G>A · rs147866099 · VCV1419830
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, eas)
Conditions
1
congenital myasthenic syndrome 18
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 -3.4 | GERP -4.5 |
| Overall | ||
| CADD | 3.329 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,874 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.00205%
33/1,613,178 alleles · ultra-rare
exomes 31/1,460,960 · genomes 2/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,640 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,831 |
| African / African-American | 0.004% | 25,001 |
| South Asian | 0.0011% | 91,044 |
| European (non-Finnish) | 0.000763% | 131,084 |
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
- SNAP25
- Protein
- p.Ser25=
- Coding
- c.75G>A
- MANE Select
- NM_130811
- dbSNP
- rs147866099
- Type
- single nucleotide variant
- Location
- chr20:10277687 (GRCh38)
- Gene constraint
- LOEUF 0.29 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.14 · 14 PDB
- Residue 25
- the t-snare coiled-coil homology 1 domain; the 'interaction with cenpf' region; an α-helix
Similar variants
- SNAP25 p.Ser25Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- SNAP25 p.Ser25Ter Uncertain significance ★ same residue
- SNAP25 p.Ala199Glu Pathogenic/Likely pathogenic ★★ same condition
- SNAP25 p.Arg198Pro Likely pathogenic ★★ same condition
- SNAP25 p.Gln197Ter Likely pathogenic ★★ same condition
- SNAP25 p.Gly43Arg Pathogenic/Likely pathogenic ★★ same condition
- SNAP25 p.Ile67Asn Pathogenic/Likely pathogenic ★★ same condition
- SNAP25 p.Lys40Glu Likely pathogenic ★★ ⚠ same condition
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/snap25-p-ser25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown