Is SYN2 p.Gln529Ter (c.1585C>T) pathogenic?

SYN2 p.Gln529Ter (c.1585C>T) is classified Uncertain significance in SYN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-29). Absent from gnomAD v4.1; Associated with schizophrenia.

What condition is associated with SYN2 p.Gln529Ter (c.1585C>T)?

SYN2 p.Gln529Ter (c.1585C>T) is associated with schizophrenia (ClinVar).

How common is SYN2 p.Gln529Ter (c.1585C>T) in the general population?

SYN2 p.Gln529Ter (c.1585C>T) is absent from gnomAD v4.1 (gnomAD).

SYN2 p.Gln529Ter

c.1585C>T · rs2470279573 · VCV1709227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

schizophrenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (12 of 13, 28 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SYN2
Protein: p.Gln529Ter
Coding: c.1585C>T
MANE Select: NM_133625
dbSNP: rs2470279573
Type: single nucleotide variant
Location: chr3:12187584 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 75.24
Residue 529: the 'disordered' region; the 'h; pro/ser-rich linker' region

Full SYN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

schizophrenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SYN2 p.Pro107Ser Uncertain significance ★ ⚠ same condition
SYN2 p.Ala54Val Benign ★★ same type
SYN2 p.Thr506Ala Benign ★★ same type
SYN2 c.1369+21G>C Uncertain significance ★ same type
SYN2 p.Ala302Gly Uncertain significance ★ same type
SYN2 p.Ala546Gly Uncertain significance ★ ⚠ same type
SYN2 p.Arg179Gln Uncertain significance ★ ⚠ same type
SYN2 p.Arg186Gln Uncertain significance ★ ⚠ same type

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/syn2-p-gln529ter (accessed [today's date]).

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