Is SYN1 p.Ala577fs (c.1729del) pathogenic?

SYN1 p.Ala577fs (c.1729del) is classified Pathogenic in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-30). No gnomAD frequency available for this variant; Associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders.

What condition is associated with SYN1 p.Ala577fs (c.1729del)?

SYN1 p.Ala577fs (c.1729del) is associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

How common is SYN1 p.Ala577fs (c.1729del) in the general population?

SYN1 p.Ala577fs (c.1729del) is no gnomAD frequency available for this variant (gnomAD).

SYN1 p.Ala577fs

Q: How is X-linked epilepsy-learning disabilities-behavior disorders syndrome inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1729del · rs2519684728 · VCV1700046

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

epilepsy, X-linked 1, with variable learning disabilities and behavior disorders

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	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 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.Ala577fs
Coding: c.1729del
MANE Select: NM_006950
dbSNP: rs2519684728
Type: Deletion
Location: chrX:47574255 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 577: 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 'd; pro-rich linker' region

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

Disease context

epilepsy, X-linked 1, with variable learning disabilities and behavior disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked epilepsy-learning disabilities-behavior disorders syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

SYN1 p.Ala577= Conflicting classifications of pathogenicity ★ same residue
SYN1 p.Asn334fs Pathogenic ★★ same condition
SYN1 p.Met1fs Pathogenic/Likely pathogenic ★★ same condition
SYN1 p.His38_Ala42del Uncertain significance ★★ same condition
SYN1 c.1056-14_1056-8del Benign ★★ same condition
SYN1 p.Ala83fs Pathogenic ★ same condition
SYN1 p.Arg430fs Pathogenic ★ same condition
SYN1 p.Asn19fs 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/syn1-p-ala577fs (accessed [today's date]).

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