Is SYN1 p.Ser551fs (c.1647_1650dup) pathogenic?

SYN1 p.Ser551fs (c.16471650dup) is classified Conflicting classifications of pathogenicity in SYN1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-09-17). Ultra-rare (gnomAD MAF 6.637e-06); Associated with intellectual disability, X-linked 50.

What condition is associated with SYN1 p.Ser551fs (c.1647_1650dup)?

SYN1 p.Ser551fs (c.1647_1650dup) is associated with intellectual disability, X-linked 50, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

How common is SYN1 p.Ser551fs (c.1647_1650dup) in the general population?

SYN1 p.Ser551fs (c.1647_1650dup) is ultra-rare (gnomAD MAF 6.637e-06) (gnomAD).

SYN1 p.Ser551fs

c.1647_1650dup · rs1456167867 · VCV1994692

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 6.637e-06)

Conditions

intellectual disability, X-linked 50

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.000664% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: SYN1
Protein: p.Ser551fs
Coding: c.1647_1650dup
MANE Select: NM_006950
dbSNP: rs1456167867
Type: Microsatellite
Location: chrX:47574333 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 551: a modified residue (phosphoserine; by pdpk1); the 'disordered' region; the 'd; pro-rich linker' region

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

Disease context

intellectual disability, X-linked 50 — 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 p.Ala550fs Pathogenic ★ same condition
SYN1 p.Ala650fs Pathogenic ★ same condition
SYN1 c.684+5_684+8del Uncertain significance ★ same condition
SYN1 p.Gln491del Conflicting classifications of pathogenicity ★ same condition
SYN1 c.1394-18_1394-15del 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

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-ser551fs (accessed [today's date]).

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