CDCP2

Chr 1

CUB domain containing protein 2

NCBI Gene: 200008 ENSG00000157211 UniProt: Q5VXM1 OMIM: 612320

CDCP2 encodes a predicted membrane-localized protein with unknown specific function. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, seizures, and brain malformations. The gene shows minimal constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.79

Clinical Summary— CDCP2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

81 VUS of 93 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.79LOEUF

pLI 0.000

Z-score -0.65

OE 1.21 (0.79–1.79)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.02Z-score

OE missense 1.00 (0.90–1.10)

270 obs / 270.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.21 (0.79–1.79)

0≤0.351.4

Missense OE?1.00 (0.90–1.10)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 14 / 11.6Missense obs/exp: 270 / 270.9Syn Z: 0.10

This gene — mechanism propensity

0.6840th %ile

GOF

0.77top 25%

LOF

0.3842th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

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

93 submitted variants in ClinVar

ClinVar

Classification Summary

VUS81

Likely Benign6

Conflicting1

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	81	0	0	81
Likely Benign	1	4	0	1	6
Benign	0	0	0	0	0
Conflicting	—				1
Total	1	85	0	1	88

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap CDCP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →