Is SYN2 p.Thr263= (c.789G>T) pathogenic?

SYN2 p.Thr263= (c.789G>T) is classified Likely benign in SYN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-24). Very rare (popmax 0.00322%, nfe); Associated with SYN2-related disorder.

What condition is associated with SYN2 p.Thr263= (c.789G>T)?

SYN2 p.Thr263= (c.789G>T) is associated with SYN2-related disorder (ClinVar).

How common is SYN2 p.Thr263= (c.789G>T) in the general population?

SYN2 p.Thr263= (c.789G>T) is very rare (popmax 0.00322%, nfe) (gnomAD).

SYN2 p.Thr263=

c.789G>T · rs750769489 · VCV3043360

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Conditions

SYN2-related disorder

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 -12	GERP -4.4
Overall
CADD	0.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,179,908 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00235% 38/1,613,854 alleles · very rare exomes 35/1,461,664 · genomes 3/152,190 · 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: SYN2
Protein: p.Thr263=
Coding: c.789G>T
MANE Select: NM_133625
dbSNP: rs750769489
Type: single nucleotide variant
Location: chr3:12161560 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 75.24
Residue 263: the 'c; actin-binding and synaptic-vesicle binding' region

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

Disease context

SYN2-related disorder

Similar variants

SYN2 c.1308+1G>A Uncertain significance same condition
SYN2 p.Ala193Val Benign same condition
SYN2 p.Ala566= Benign same condition
SYN2 p.Lys128Arg Benign same condition
SYN2 p.Ser540= Benign same condition
SYN2 c.1370-4del Likely benign same condition
SYN2 p.Ala54Val Benign ★★ same type
SYN2 p.Thr506Ala Benign ★★ 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-thr263 (accessed [today's date]).

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