Is SYN1 p.Ser568= (c.1704C>G) pathogenic?

SYN1 p.Ser568= (c.1704C>G) is classified Likely benign in SYN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-03). Very rare (popmax 0.00312%, amr); Associated with Inborn genetic diseases.

What condition is associated with SYN1 p.Ser568= (c.1704C>G)?

SYN1 p.Ser568= (c.1704C>G) is associated with Inborn genetic diseases, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

How common is SYN1 p.Ser568= (c.1704C>G) in the general population?

SYN1 p.Ser568= (c.1704C>G) is very rare (popmax 0.00312%, amr) (gnomAD).

SYN1 p.Ser568=

c.1704C>G · rs1357882662 · VCV1778408

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00312%, amr)

Conditions

Inborn genetic diseases

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 -5.9
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00312% Admixed American · 1/32,021 alleles

Overall 9.06e-05% 1/1,103,975 alleles · very rare exomes 0/991,266 · genomes 1/112,709 · joint denominator

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: SYN1
Protein: p.Ser568=
Coding: c.1704C>G
MANE Select: NM_006950
dbSNP: rs1357882662
Type: single nucleotide variant
Location: chrX:47574280 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 568: a modified residue (phosphoserine; by camk2); 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

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.Arg420Gln Likely pathogenic ★★ ⚠ same condition
SYN1 p.Arg422Ter Pathogenic ★★ same condition
SYN1 p.Gln483Ter Pathogenic ★★ same condition
SYN1 p.Gln555Ter Pathogenic ★★ same condition
SYN1 p.Glu121Ter Pathogenic/Likely 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-ser568 (accessed [today's date]).

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