Is SNAP25 p.Arg8Ser (c.22C>A) pathogenic?

SNAP25 p.Arg8Ser (c.22C>A) is classified Uncertain significance in SNAP25 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). AlphaMissense: likely pathogenic (0.8761); No allele count reported in gnomAD v4.1 (AN 1,605,896); Associated with congenital myasthenic syndrome 18.

What condition is associated with SNAP25 p.Arg8Ser (c.22C>A)?

SNAP25 p.Arg8Ser (c.22C>A) is associated with congenital myasthenic syndrome 18 (ClinVar).

How common is SNAP25 p.Arg8Ser (c.22C>A) in the general population?

SNAP25 p.Arg8Ser (c.22C>A) is no allele count reported in gnomAD v4.1 (AN 1,605,896) (gnomAD).

What do computational predictors say about SNAP25 p.Arg8Ser (c.22C>A)?

AlphaMissense predicts likely pathogenic (score 0.8761) — an in-silico prediction, not a clinical call.

SNAP25 p.Arg8Ser

c.22C>A · rs555461700 · VCV1720776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8761 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,896)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 18

Computational evidence

Protein change
AlphaMissense	0.8761	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 9,233 bp · p 0.00082 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,896). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SNAP25
Protein: p.Arg8Ser
Coding: c.22C>A
MANE Select: NM_130811
dbSNP: rs555461700
Type: single nucleotide variant
Location: chr20:10275513 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 14 PDB
Residue 8: the 'interaction with cenpf' region; an α-helix; the 'disordered' region

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

Disease context

congenital myasthenic syndrome 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SNAP25 p.Arg8His Uncertain significance ★★ ⚠ same residue
SNAP25 p.Arg8Cys Uncertain significance ★ ⚠ same residue
SNAP25 p.Arg8= Likely benign ★ 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

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-arg8ser (accessed [today's date]).

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