Is SNAP25 p.Asp51= (c.153T>C) pathogenic?

SNAP25 p.Asp51= (c.153T>C) is classified Likely benign in SNAP25 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-04). Very rare (popmax 0.00017%, nfe).

How common is SNAP25 p.Asp51= (c.153T>C) in the general population?

SNAP25 p.Asp51= (c.153T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

SNAP25 p.Asp51=

c.153T>C · VCV4944351

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 7.8	GERP 2.4, phastCons 1
Overall
CADD	14.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,004 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,788 alleles · very rare exomes 3/1,460,414 · genomes 0/152,374 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)grpmax	0.00017%	589,501

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp51=
Coding: c.153T>C
MANE Select: NM_130811
Type: single nucleotide variant
Location: chr20:10284762 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 14 PDB
Residue 51: 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

Similar variants

SNAP25 p.Ala199Glu Pathogenic/Likely pathogenic ★★ same type
SNAP25 p.Ala199Gly Pathogenic/Likely pathogenic ★★ same type
SNAP25 p.Arg198Pro Likely pathogenic ★★ same type
SNAP25 p.Gln197Ter Likely pathogenic ★★ same type
SNAP25 p.Gly43Arg Pathogenic/Likely pathogenic ★★ same type
SNAP25 p.Ile67Asn Pathogenic/Likely pathogenic ★★ same type
SNAP25 p.Lys40Glu Likely pathogenic ★★ ⚠ same type
SNAP25 p.Met71Thr Pathogenic/Likely pathogenic ★★ ⚠ same type

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-asp51 (accessed [today's date]).

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