Is SYNJ2 p.Ala401Val (c.1202C>T) pathogenic?

SYNJ2 p.Ala401Val (c.1202C>T) is classified Uncertain significance in SYNJ2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely pathogenic (0.8238); Very rare (popmax 0.00892%, eas).

How common is SYNJ2 p.Ala401Val (c.1202C>T) in the general population?

SYNJ2 p.Ala401Val (c.1202C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about SYNJ2 p.Ala401Val (c.1202C>T)?

AlphaMissense predicts likely pathogenic (score 0.8238) — an in-silico prediction, not a clinical call.

SYNJ2 p.Ala401Val

c.1202C>T · VCV3451995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8238 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8238	likely pathogenic
REVEL	0.663	pathogenic-leaning
SaProt	LLR -10.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 114 kb · p 0.16 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00892% East Asian · 4/44,850 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00149% 24/1,613,466 alleles · very rare exomes 19/1,461,190 · genomes 5/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,212
African / African-American	0.00533%	18,754
Remaining individualsnot grpmax-eligible	0.0016%	62,460
European (non-Finnish)	0.00119%	84,267
South Asian	0.0011%	91,068

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: SYNJ2
Protein: p.Ala401Val
Coding: c.1202C>T
MANE Select: NM_003898
Type: single nucleotide variant
Location: chr6:158063865 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.47 · 1 PDB
Residue 401: the sac domain

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-ala401val (accessed [today's date]).

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