Is SYN1 p.Asp313= (c.939C>T) pathogenic?

SYN1 p.Asp313= (c.939C>T) is classified Likely benign in SYN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.0494%, nfe); Associated with History of neurodevelopmental disorder.

What condition is associated with SYN1 p.Asp313= (c.939C>T)?

SYN1 p.Asp313= (c.939C>T) is associated with History of neurodevelopmental disorder, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

How common is SYN1 p.Asp313= (c.939C>T) in the general population?

SYN1 p.Asp313= (c.939C>T) is ultra-rare (popmax 0.0494%, nfe) (gnomAD).

SYN1 p.Asp313=

c.939C>T · rs373928763 · VCV465102

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0494%, nfe)

Conditions

History of neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.90 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.9
Overall
CADD	4.297	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0494% European (non-Finnish) · 442/895,323 alleles

Filtering AF 0.0456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.044%

Overall 0.0393% 476/1,210,166 alleles · ultra-rare exomes 453/1,098,254 · genomes 23/111,912 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0494%	2,026
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Admixed American	0.0196%	5,090
African / African-American	0.0157%	6,351

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: SYN1
Protein: p.Asp313=
Coding: c.939C>T
MANE Select: NM_006950
dbSNP: rs373928763
Type: single nucleotide variant
Location: chrX:47576539 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 313: the 'c; actin-binding and synaptic-vesicle binding' region

Full SYN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

History of neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epilepsy, X-linked 1, with variable learning disabilities and behavior disorders

Similar variants

SYN1 c.528-2A>T Pathogenic/Likely pathogenic ★★ same condition
SYN1 c.838-2A>G Likely pathogenic ★★ same condition
SYN1 p.Arg234Ter Pathogenic ★★ same condition
SYN1 p.Arg420Gln Likely pathogenic ★★ ⚠ same condition
SYN1 p.Arg422Ter Pathogenic ★★ same condition
SYN1 p.Gln483Ter Pathogenic ★★ same condition
SYN1 p.Gln555Ter Pathogenic ★★ same condition
SYN1 p.Glu121Ter Pathogenic/Likely pathogenic ★★ same condition

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/syn1-p-asp313 (accessed [today's date]).

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