RAVER2

Chr 1

ribonucleoprotein, PTB binding 2

NCBI Gene: 55225 ENSG00000162437 UniProt: Q9HCJ3 OMIM: 609953

RAVER2 encodes an RNA-binding protein that binds single-stranded nucleic acids and localizes to the cytoplasm and nucleus. Mutations cause autosomal recessive neurodevelopmental disorder with seizures, spasticity, and brain abnormalities. The gene shows moderate tolerance to loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.81

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.000

Z-score 2.40

OE 0.55 (0.38–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.72Z-score

OE missense 0.89 (0.81–0.98)

299 obs / 336.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.38–0.81)

0≤0.351.4

Missense OE?0.89 (0.81–0.98)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 18 / 32.8Missense obs/exp: 299 / 336.2Syn Z: 0.21

Background carrier burden — how many people carry a rare variant somewhere in RAVER2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

852 rare PASS variants

Rare truncating (LoF)

1 in 1,100

132 rare PASS variants

Rare synonymous (reference)

1 in 130

326 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RAVER2. 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 130	1 in 1,200
South Asian	~43k	1 in 67	1 in 700
Remaining (unassigned)	~30k	1 in 68	1 in 2,000
European (Finnish)	~27k	1 in 430	1 in 5,300
Admixed American	~22k	1 in 82	≈ 1 in 6,800
African / African American	~21k	1 in 78	1 in 740
East Asian	~20k	1 in 69	1 in 700
Ashkenazi Jewish	~13k	1 in 740	1 in 1,500
Middle Eastern	~2,884	1 in 77	≈ 1 in 960

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): 7 of 12 coding exons well covered in gnomAD exomes; exons 1, 2, 6, 7, 11 marginal. Genomes: all 12.? see exons ↓