Is SNAP25 p.Glu73= (c.219A>G) pathogenic?

SNAP25 p.Glu73= (c.219A>G) is classified Uncertain significance in SNAP25 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-07). Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 18.

What condition is associated with SNAP25 p.Glu73= (c.219A>G)?

SNAP25 p.Glu73= (c.219A>G) is associated with congenital myasthenic syndrome 18 (ClinVar).

How common is SNAP25 p.Glu73= (c.219A>G) in the general population?

SNAP25 p.Glu73= (c.219A>G) is absent from gnomAD v4.1 (gnomAD).

SNAP25 p.Glu73=

c.219A>G · rs1051273 · VCV2911459

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital myasthenic syndrome 18

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 11	GERP 1.3, phastCons 1
Overall
CADD	9.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SNAP25
Protein: p.Glu73=
Coding: c.219A>G
MANE Select: NM_130811
dbSNP: rs1051273
Type: single nucleotide variant
Location: chr20:10293216 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 14 PDB
Residue 73: the t-snare coiled-coil homology 1 domain; the 'interaction with cenpf' region; an α-helix

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.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
SNAP25 p.Ala2Thr Uncertain significance ★★ ⚠ 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-glu73 (accessed [today's date]).

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