Is SYNJ2 p.Ala60Val (c.179C>T) pathogenic?

SYNJ2 p.Ala60Val (c.179C>T) is classified Uncertain significance in SYNJ2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely benign (0.3359); Rare (popmax 0.33%, mid); Associated with Meniere disease.

What condition is associated with SYNJ2 p.Ala60Val (c.179C>T)?

SYNJ2 p.Ala60Val (c.179C>T) is associated with Meniere disease (ClinVar).

How common is SYNJ2 p.Ala60Val (c.179C>T) in the general population?

SYNJ2 p.Ala60Val (c.179C>T) is rare (popmax 0.33%, mid) (gnomAD).

What do computational predictors say about SYNJ2 p.Ala60Val (c.179C>T)?

AlphaMissense predicts likely benign (score 0.3359) — an in-silico prediction, not a clinical call.

SYNJ2 p.Ala60Val

c.179C>T · rs143362296 · VCV3238895

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3359 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.33%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Meniere disease

Computational evidence

Protein change
AlphaMissense	0.3359	likely benign
REVEL	0.456	indeterminate
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 114 kb · p 0.16 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.33% Middle Eastern · 20/6,060 alleles

Filtering AF 0.239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.225% 3,638/1,613,908 alleles · rare exomes 3,267/1,461,698 · genomes 371/152,210 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.43%	70
Finnishnot grpmax-eligible	0.525%	190
Middle Easterngrpmax	0.33%	303
European (non-Finnish)	0.246%	406
Remaining individualsnot grpmax-eligible	0.235%	425
South Asian	0.163%	615
Admixed American	0.06%	1,667
African / African-American	0.0413%	2,419
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
East Asian	0.00223%	44,876

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala60Val
Coding: c.179C>T
MANE Select: NM_003898
dbSNP: rs143362296
Type: single nucleotide variant
Location: chr6:158017255 (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

Disease context

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

Similar variants

SYNJ2 p.Arg546Gln Uncertain significance ★ ⚠ same condition
SYNJ2 p.Gly187Arg Uncertain significance ★ ⚠ same condition
SYNJ2 p.Val301Met Uncertain significance same condition
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

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-ala60val (accessed [today's date]).

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