Is SYN1 p.Arg186fs (c.554_555insA) pathogenic?

SYN1 p.Arg186fs (c.554555insA) is classified Pathogenic in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). 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.Arg186fs (c.554_555insA)?

SYN1 p.Arg186fs (c.554_555insA) is associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

How common is SYN1 p.Arg186fs (c.554_555insA) in the general population?

SYN1 p.Arg186fs (c.554_555insA) is no gnomAD frequency available for this variant (gnomAD).

SYN1 p.Arg186fs

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.554_555insA · rs2519705505 · VCV2133935

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 4 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP -0.92, 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.Arg186fs
Coding: c.554_555insA
MANE Select: NM_006950
dbSNP: rs2519705505
Type: Insertion
Location: chrX:47605352 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 186: 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.Arg186His Uncertain significance ★★ ⚠ same residue
SYN1 p.Arg186Cys Uncertain significance ★ ⚠ same residue
SYN1 c.528-2A>T Pathogenic/Likely pathogenic ★★ same condition
SYN1 c.838-2A>G Likely pathogenic ★★ same condition
SYN1 p.Arg234Ter Pathogenic ★★ same condition
SYN1 p.Arg420fs Pathogenic ★★ same condition
SYN1 p.Arg420Gln Likely pathogenic ★★ ⚠ same condition
SYN1 p.Arg422Ter 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-arg186fs (accessed [today's date]).

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