Is SYNJ2 p.Val454Ala (c.1361T>C) pathogenic?

SYNJ2 p.Val454Ala (c.1361T>C) is classified Uncertain significance in SYNJ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.1936); Absent from gnomAD v4.1.

How common is SYNJ2 p.Val454Ala (c.1361T>C) in the general population?

SYNJ2 p.Val454Ala (c.1361T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SYNJ2 p.Val454Ala (c.1361T>C)?

AlphaMissense predicts likely benign (score 0.1936) — an in-silico prediction, not a clinical call.

SYNJ2 p.Val454Ala

c.1361T>C · rs771215497 · VCV3172799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1936 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1936	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP -2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 114 kb · p 0.16 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: SYNJ2
Protein: p.Val454Ala
Coding: c.1361T>C
MANE Select: NM_003898
dbSNP: rs771215497
Type: single nucleotide variant
Location: chr6:158064827 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.47 · 1 PDB

Full SYNJ2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SYNJ2 p.Asp1071Glu Uncertain significance ★★ ⚠ same type
SYNJ2 p.Val420Ala Likely benign ★★ same type
SYNJ2 p.Ala1072Thr Uncertain significance ★ ⚠ same type
SYNJ2 p.Ala111Asp Uncertain significance ★ ⚠ same type
SYNJ2 p.Ala1186Thr Uncertain significance ★ ⚠ same type
SYNJ2 p.Ala1199Thr Uncertain significance ★ ⚠ same type
SYNJ2 p.Ala1274Gly Uncertain significance ★ ⚠ same type
SYNJ2 p.Ala1298Ser 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/synj2-p-val454ala (accessed [today's date]).

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