Is SYN2 p.Ala193Val (c.578C>T) pathogenic?

SYN2 p.Ala193Val (c.578C>T) is classified Benign in SYN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-24). AlphaMissense: likely benign (0.223); Rare (popmax 0.259%, eas); Associated with SYN2-related disorder.

What condition is associated with SYN2 p.Ala193Val (c.578C>T)?

SYN2 p.Ala193Val (c.578C>T) is associated with SYN2-related disorder (ClinVar).

How common is SYN2 p.Ala193Val (c.578C>T) in the general population?

SYN2 p.Ala193Val (c.578C>T) is rare (popmax 0.259%, eas) (gnomAD).

What do computational predictors say about SYN2 p.Ala193Val (c.578C>T)?

AlphaMissense predicts likely benign (score 0.223) — an in-silico prediction, not a clinical call.

SYN2 p.Ala193Val

c.578C>T · rs191537003 · VCV3042477

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.223 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.259%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

SYN2-related disorder

Computational evidence

Protein change
AlphaMissense	0.223	likely benign
REVEL	0.506	indeterminate
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 186 kb · p 0.66 · regional, not allelic
Overall
CADD	24.0	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 0.259% East Asian · 116/44,874 alleles

Filtering AF 0.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.206%

Overall 0.0104% 168/1,613,960 alleles · rare exomes 143/1,461,688 · genomes 25/152,272 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.259%	387
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Admixed American	0.005%	20,007
African / African-American	0.00133%	75,026
European (non-Finnish)	0.00127%	78,659

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.Ala193Val
Coding: c.578C>T
MANE Select: NM_133625
dbSNP: rs191537003
Type: single nucleotide variant
Location: chr3:12145729 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 75.24
Residue 193: 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.Ala566= Benign same condition
SYN2 p.Lys128Arg Benign same condition
SYN2 p.Ser540= Benign same condition
SYN2 p.Thr263= Likely 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-ala193val (accessed [today's date]).

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