Is SYNJ1 p.Arg97Ter (c.289C>T) pathogenic?

SYNJ1 p.Arg97Ter (c.289C>T) is classified Pathogenic in SYNJ1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-03). Very rare (popmax 0.00134%, afr); Associated with SYNJ1-related disorder.

What condition is associated with SYNJ1 p.Arg97Ter (c.289C>T)?

SYNJ1 p.Arg97Ter (c.289C>T) is associated with SYNJ1-related disorder (ClinVar).

How common is SYNJ1 p.Arg97Ter (c.289C>T) in the general population?

SYNJ1 p.Arg97Ter (c.289C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

SYNJ1 p.Arg97Ter

c.289C>T · rs2042344677 · VCV1206765

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

SYNJ1-related disorder

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	predicted	premature termination codon in exon 4 of 33
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 0.84, phastCons 1
Overall
CADD	39.0	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

Grpmax group 0.00134% African / African-American · 1/74,864 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,928 alleles · very rare exomes 3/1,461,862 · genomes 1/152,066 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,864
European (non-Finnish)	0.000254%	393,343

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: SYNJ1
Protein: p.Arg97Ter
Coding: c.289C>T
MANE Select: NM_203446
dbSNP: rs2042344677
Type: single nucleotide variant
Location: chr21:32700028 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 5 PDB

Full SYNJ1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SYNJ1-related disorder

Similar variants

SYNJ1 p.Arg97Gln Uncertain significance ★★ same residue
SYNJ1 p.Arg709Ter Pathogenic/Likely pathogenic ★★ same condition
SYNJ1 c.3698-2A>T Likely pathogenic ★ same condition
SYNJ1 p.Trp561Arg Uncertain significance same condition
SYNJ1 p.Tyr365fs Pathogenic/Likely pathogenic ★★ same condition
SYNJ1 c.1201-2A>G Likely pathogenic ★★ same type
SYNJ1 c.2461+2T>C Likely pathogenic ★★ same type
SYNJ1 c.3478+1G>A Likely pathogenic ★★ 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/synj1-p-arg97ter (accessed [today's date]).

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