SYAP1

Chr X

synapse associated protein 1

Also known as: BSTA, PRO3113, SAP47

NCBI Gene: 94056 ENSG00000169895 UniProt: Q96A49

The SYAP1 protein promotes mTORC2-mediated phosphorylation of AKT1 and plays a role in adipocyte differentiation and cellular responses to growth factors. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants (pLI 0.94, LOEUF 0.35), indicating that complete loss of function is likely pathogenic.

ResearchSummary from RefSeq, UniProt

Involved in several processes, including TORC2 signaling; cellular response to epidermal growth factor stimulus; and cellular response to peptide hormone stimulus. Located in several cellular components, including Golgi apparatus; cytoplasmic side of plasma membrane; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 0.35

Clinical Summary— SYAP1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

29 VUS of 110 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.943

Z-score 3.15

OE 0.07 (0.03–0.35)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.16Z-score

OE missense 0.71 (0.60–0.85)

90 obs / 126.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.35)

0≤0.351.4

Missense OE?0.71 (0.60–0.85)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 1 / 13.5Missense obs/exp: 90 / 126.7Syn Z: 0.34

ClinVar Variant Classifications

110 submitted variants in ClinVar

ClinVar

Classification Summary

VUS29

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	29	0	29
Likely Benign	3	1	4
Benign	0	0	0
Total	32	1	33

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

81 pathogenic / likely-pathogenic (of 90) ClinVar copy-number / structural variants overlap SYAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →