SMAP2

Chr 1

small ArfGAP2

Also known as: SMAP1L

NCBI Gene: 64744 ENSG00000084070 UniProt: Q8WU79 OMIM: 616916

SMAP2 encodes a GTPase activating protein that regulates ARF1 and ARF6, functioning in clathrin-dependent retrograde transport from early endosomes to the trans-Golgi network. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy. The gene is moderately constrained against loss-of-function variants (LOEUF 0.55).

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable GTPase activator activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.55

Clinical Summary— SMAP2

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

📋

ClinVar Variants

1 VUS of 21 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.55LOEUF

pLI 0.018

Z-score 3.28

OE 0.31 (0.18–0.55)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.52Z-score

OE missense 0.73 (0.64–0.82)

180 obs / 247.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.18–0.55)

0≤0.351.4

Missense OE?0.73 (0.64–0.82)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 8 / 26.1Missense obs/exp: 180 / 247.2Syn Z: 1.28

This gene — mechanism propensity

0.6745th %ile

GOF

0.5169th %ile

LOF

0.2872th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

21 submitted variants in ClinVar

ClinVar

Classification Summary

VUS1

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	—	—	—	—	0
Likely Pathogenic	—	—	—	—	0
VUS	—	—	—	—	1
Likely Benign	—	—	—	—	1
Benign	—	—	—	—	0
Total	—				2

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

8 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap SMAP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →