Is SYN1 p.Ala550Phe (c.1648_1649delinsTT) pathogenic?

SYN1 p.Ala550Phe (c.16481649delinsTT) is classified Uncertain significance in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). No gnomAD frequency available for this variant; Associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders.

What condition is associated with SYN1 p.Ala550Phe (c.1648_1649delinsTT)?

SYN1 p.Ala550Phe (c.1648_1649delinsTT) is associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

How common is SYN1 p.Ala550Phe (c.1648_1649delinsTT) in the general population?

SYN1 p.Ala550Phe (c.1648_1649delinsTT) is no gnomAD frequency available for this variant (gnomAD).

SYN1 p.Ala550Phe

Q: How is X-linked epilepsy-learning disabilities-behavior disorders syndrome inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1648_1649delinsTT · rs2057770383 · VCV944089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.5	phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,483 bp · p 0.025 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SYN1
Protein: p.Ala550Phe
Coding: c.1648_1649delinsTT
MANE Select: NM_006950
dbSNP: rs2057770383
Type: Indel
Location: chrX:47574335 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 550: the 'disordered' region; a UniProt-annotated variant site (in xlid50; uncertain significance; no effect on phosphorylation by camk2 and mapk1; has no effect on axon elongation when tested in syn1-knockout mouse neurons; slightly reduced protein targeting to presynapse); the 'd; pro-rich linker' region

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

Disease context

epilepsy, X-linked 1, with variable learning disabilities and behavior disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked epilepsy-learning disabilities-behavior disorders syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

SYN1 p.Ala550fs Pathogenic ★ same residue
SYN1 p.Ala550Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
SYN1 p.Gln423_Arg424delinsHisTrp Uncertain significance ★ same condition
SYN1 c.1982+8_1982+20delinsT Likely benign ★ same condition
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.Arg420fs 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-ala550phe (accessed [today's date]).

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