CLASP2

Chr 3

cytoplasmic linker associated protein 2

The protein stabilizes microtubules at their growing ends and is essential for proper chromosome alignment during cell division and microtubule organization in migrating cells. Mutations cause neurodevelopmental disorders with intellectual disability and epilepsy, typically with autosomal dominant inheritance. This gene is extremely intolerant to loss-of-function mutations (pLI ~1.0), indicating that even single gene copies are critical for normal neurological development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.20
Clinical SummaryCLASP2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 116 VUS of 199 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 7.49
OE 0.12 (0.070.20)
Highly constrained

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

Missense Constraint
3.87Z-score
OE missense 0.61 (0.560.66)
466 obs / 768.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.12 (0.070.20)
00.351.4
Missense OE0.61 (0.560.66)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 10 / 84.2Missense obs/exp: 466 / 768.0Syn Z: 0.13
DN
0.5673th %ile
GOF
0.4776th %ile
LOF
0.66top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.20

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

199 submitted variants in ClinVar

Classification Summary

Pathogenic17
VUS116
Likely Benign16
Benign11
17
Pathogenic
116
VUS
16
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
0
0
0
VUS
0
112
4
0
116
Likely Benign
0
1
4
11
16
Benign
0
4
2
5
11
Total01172716160

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

View in ClinVar →

Protein Context — Lollipop Plot

CLASP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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