ADAP1

Chr 7

ArfGAP with dual PH domains 1

Also known as: CENTA1, GCS1L, p42IP4

NCBI Gene: 11033 ENSG00000105963 UniProt: O75689 OMIM: 608114

ADAP1 encodes a GTPase-activating protein that regulates ADP ribosylation factor family proteins and controls the incorporation of CD63 and CD9 into multivesicular bodies. Mutations cause autosomal recessive developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability. The gene shows significant constraint against loss-of-function variants (LOEUF 0.44), suggesting intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, UniProt

Enables GTPase activator activity. Predicted to be involved in cell surface receptor signaling pathway. Located in cytosol; nucleus; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.44

Clinical Summary— ADAP1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.53) — some intolerance to loss-of-function variants.

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ClinVar Variants

51 VUS of 79 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.533

Z-score 3.59

OE 0.21 (0.11–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.89Z-score

OE missense 0.83 (0.74–0.94)

188 obs / 225.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.11–0.44)

0≤0.351.4

Missense OE?0.83 (0.74–0.94)

0≤0.61.4

Synonymous OE?1.65

0≤1.21.6

LoF obs/exp: 5 / 24.0Missense obs/exp: 188 / 225.5Syn Z: -4.92

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign3

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	51	0	0	51
Likely Benign	2	0	1	3
Benign	0	1	1	2
Total	53	1	2	56

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap ADAP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →