ACAP2

Chr 3

ArfGAP with coiled-coil, ankyrin repeat and PH domains 2

Also known as: CENTB2, CNT-B2

NCBI Gene: 23527 ENSG00000114331 UniProt: Q15057

Enables GTPase activator activity. Acts upstream of or within actin filament-based process. Located in plasma membrane and ruffle. [provided by Alliance of Genome Resources, Jun 2026]

Research

Enables GTPase activator activity. Acts upstream of or within actin filament-based process. Located in plasma membrane and ruffle. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.32

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.32LOEUF

pLI 0.923

Z-score 5.42

OE 0.19 (0.12–0.32)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.22Z-score

OE missense 0.55 (0.49–0.61)

224 obs / 406.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.19 (0.12–0.32)

0≤0.351.4

Missense OE?0.55 (0.49–0.61)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 10 / 52.3Missense obs/exp: 224 / 406.7Syn Z: 1.55

Background carrier burden — how many people carry a rare variant somewhere in ACAP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

794 rare PASS variants

Rare truncating (LoF)

1 in 2,900

91 rare PASS variants

Rare synonymous (reference)

1 in 140

343 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACAP2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 160	1 in 2,900
South Asian	~43k	1 in 94	1 in 4,900
Remaining (unassigned)	~30k	1 in 150	1 in 4,000
European (Finnish)	~27k	1 in 440	1 in 3,300
Admixed American	~22k	1 in 140	1 in 3,000
African / African American	~21k	1 in 130	1 in 3,100
East Asian	~20k	1 in 110	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 260	1 in 1,700
Middle Eastern	~2,884	1 in 120	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 20 of 23 coding exons well covered in gnomAD exomes; exons 8, 18, 23 marginal. Genomes: all 23.? see exons ↓