EVA1B

Chr 1

eva-1 homolog B

Also known as: C1orf78, FAM176B

NCBI Gene: 55194 ENSG00000142694 UniProt: Q9NVM1

The EVA1B protein is predicted to be located in cellular membranes, though its specific function remains unclear. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. This gene shows moderate constraint against loss-of-function mutations, suggesting it plays an important role in normal cellular function.

ResearchSummary from RefSeq

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

ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.69

Clinical Summary— EVA1B

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.73) — some intolerance to loss-of-function variants.

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ClinVar Variants

22 VUS of 24 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.69LOEUF

pLI 0.729

Z-score 1.92

OE 0.00 (0.00–0.69)

Moderately constrained

Typical tolerance to LoF variation

Missense Constraint?

0.78Z-score

OE missense 0.79 (0.67–0.95)

87 obs / 109.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.69)

0≤0.351.4

Missense OE?0.79 (0.67–0.95)

0≤0.61.4

Synonymous OE?0.72

0≤1.21.6

LoF obs/exp: 0 / 4.3Missense obs/exp: 87 / 109.9Syn Z: 1.66

This gene — mechanism propensity

0.6064th %ile

GOF

0.73top 25%

LOF

0.4726th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

24 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	22	22
Likely Benign	2	2
Benign	0	0
Total	24	24

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap EVA1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →