Is SNAP25 p.Asp172= (c.516T>C) pathogenic?

SNAP25 p.Asp172= (c.516T>C) is classified Likely benign in SNAP25 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-14). Very rare (popmax 0.00267%, afr); Associated with congenital myasthenic syndrome 18.

What condition is associated with SNAP25 p.Asp172= (c.516T>C)?

SNAP25 p.Asp172= (c.516T>C) is associated with congenital myasthenic syndrome 18 (ClinVar).

How common is SNAP25 p.Asp172= (c.516T>C) in the general population?

SNAP25 p.Asp172= (c.516T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

SNAP25 p.Asp172=

c.516T>C · rs1250459700 · VCV1952367

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 0.45	GERP -1.2, phastCons 1
Overall
CADD	8.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,892 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,834 alleles · very rare exomes 2/1,461,706 · genomes 1/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,446
European (non-Finnish)	8.47e-05%	1,179,948

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.Asp172=
Coding: c.516T>C
MANE Select: NM_130811
dbSNP: rs1250459700
Type: single nucleotide variant
Location: chr20:10299376 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 14 PDB
Residue 172: the t-snare coiled-coil homology 2 domain

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.Asp172Asn Conflicting classifications of pathogenicity ★ ⚠ 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-asp172 (accessed [today's date]).

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