Is SYN1 p.Ala676fs (c.2026del) pathogenic?

SYN1 p.Ala676fs (c.2026del) is classified Likely pathogenic in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-06-01). No gnomAD frequency available for this variant.

How common is SYN1 p.Ala676fs (c.2026del) in the general population?

SYN1 p.Ala676fs (c.2026del) is no gnomAD frequency available for this variant (gnomAD).

SYN1 p.Ala676fs

c.2026del · rs1064797369 · VCV425495

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.6	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: SYN1
Protein: p.Ala676fs
Coding: c.2026del
MANE Select: NM_006950
dbSNP: rs1064797369
Type: Deletion
Location: chrX:47572956 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 676: the 'disordered' region; a UniProt-annotated variant site (in xlid50; affects excitatory and inhibitory synaptic transmission leading to neuronal hyperexcitability; fails to rescue defective synaptic vesicle exocytosis in syn1-knockout mouse neurons; results in severely decreased phosphorylation by camk2 and mapk1; results in delayed axon elongation when tested in syn1-knockout mouse neurons; severely reduced interaction with syn2; has no effect on protein targeting to presynapse); the 'e' region

Full SYN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SYN1 p.Ala676= Conflicting classifications of pathogenicity ★ same residue
SYN1 p.Ala676Ser Uncertain significance ★ ⚠ same residue
SYN1 p.Asn334fs Pathogenic ★★ same type
SYN1 p.Met1fs Pathogenic/Likely pathogenic ★★ same type
SYN1 p.His38_Ala42del Uncertain significance ★★ same type
SYN1 c.1056-14_1056-8del Benign ★★ same type
SYN1 c.980+43_981del Pathogenic ★ same type
SYN1 p.Ala577fs 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/syn1-p-ala676fs (accessed [today's date]).

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