Is SNAP25 p.Ala2= (c.6C>T) pathogenic?

SNAP25 p.Ala2= (c.6C>T) is classified Likely benign in SNAP25 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-30). Rare (popmax 0.129%, afr); Associated with Inborn genetic diseases.

What condition is associated with SNAP25 p.Ala2= (c.6C>T)?

SNAP25 p.Ala2= (c.6C>T) is associated with Inborn genetic diseases, congenital myasthenic syndrome 18 (ClinVar).

How common is SNAP25 p.Ala2= (c.6C>T) in the general population?

SNAP25 p.Ala2= (c.6C>T) is rare (popmax 0.129%, afr) (gnomAD).

SNAP25 p.Ala2=

c.6C>T · rs11547858 · VCV542730

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.129%, afr)

Conditions

Inborn genetic diseases

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 -8.4	GERP -4.8
Overall
CADD	4.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% African / African-American · 97/74,922 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00705% 113/1,603,960 alleles · rare exomes 59/1,451,640 · genomes 54/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.129%	772
Admixed American	0.0119%	8,423
Remaining individualsnot grpmax-eligible	0.0113%	8,875
European (non-Finnish)	0.00017%	587,437

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.Ala2=
Coding: c.6C>T
MANE Select: NM_130811
dbSNP: rs11547858
Type: single nucleotide variant
Location: chr20:10275497 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 14 PDB
Residue 2: the 'interaction with cenpf' region; the 'disordered' region

Full SNAP25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 18

Similar variants

SNAP25 p.Ala2Thr 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
SNAP25 p.Met71Thr Pathogenic/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-ala2 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown