Is SYN1 p.Asp382fs (c.1144del) pathogenic?

SYN1 p.Asp382fs (c.1144del) is classified Pathogenic in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). Associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders.

What condition is associated with SYN1 p.Asp382fs (c.1144del)?

SYN1 p.Asp382fs (c.1144del) is associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

SYN1 p.Asp382fs

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.1144del · VCV3729491

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 9 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	phastCons 1

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

Variant & gene context

Gene: SYN1
Protein: p.Asp382fs
Coding: c.1144del
MANE Select: NM_006950
Type: Deletion
Location: chrX:47576145 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 382: the 'c; actin-binding and synaptic-vesicle binding' 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.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.Ala577fs Pathogenic ★ 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-asp382fs (accessed [today's date]).

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