Is SYN1 p.Val569= (c.1707C>T) pathogenic?

SYN1 p.Val569= (c.1707C>T) is classified Likely benign in SYN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-30). Very rare (popmax 0.00192%, afr); Associated with SYN1-related disorder.

What condition is associated with SYN1 p.Val569= (c.1707C>T)?

SYN1 p.Val569= (c.1707C>T) is associated with SYN1-related disorder (ClinVar).

How common is SYN1 p.Val569= (c.1707C>T) in the general population?

SYN1 p.Val569= (c.1707C>T) is very rare (popmax 0.00192%, afr) (gnomAD).

SYN1 p.Val569=

c.1707C>T · rs1033238239 · VCV3054210

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00192%, afr)

Conditions

SYN1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	phastCons 1
Overall
CADD	4.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00192% African / African-American · 1/52,206 alleles

Overall 9.06e-05% 1/1,104,299 alleles · very rare exomes 0/991,556 · genomes 1/112,743 · 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.Val569=
Coding: c.1707C>T
MANE Select: NM_006950
dbSNP: rs1033238239
Type: single nucleotide variant
Location: chrX:47574277 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 569: 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

SYN1-related disorder

Similar variants

SYN1 p.Val569Ile Uncertain significance ⚠ same residue
SYN1 c.838-2A>G Likely pathogenic ★★ same condition
SYN1 p.Gln555Ter Pathogenic ★★ same condition
SYN1 p.Ala607Gly Uncertain significance ★★ ⚠ same condition
SYN1 c.684+1G>T Likely pathogenic ★ same condition
SYN1 p.Met14Thr Uncertain significance ★ ⚠ same condition
SYN1 p.Met232Leu Uncertain significance ★ ⚠ same condition
SYN1 p.Met1Ile Uncertain significance 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-val569 (accessed [today's date]).

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