VWA8

Chr 13AD

von Willebrand factor A domain containing 8

Also known as: KIAA0564, P7BP2, RP97

The VWA8 protein exhibits ATPase activity and localizes to mitochondria and peroxisomes. Mutations cause retinitis pigmentosa 97, which follows autosomal dominant inheritance. The gene shows extremely high constraint against loss-of-function variants (pLI essentially 1.0), indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ADLOEUF 1.151 OMIM phenotype
Clinical SummaryVWA8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 177 VUS of 295 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.15LOEUF
pLI 0.000
Z-score 0.20
OE 0.98 (0.841.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.21Z-score
OE missense 1.02 (0.971.07)
1028 obs / 1009.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.98 (0.841.15)
00.351.4
Missense OE1.02 (0.971.07)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 107 / 109.3Missense obs/exp: 1028 / 1009.6Syn Z: -0.29

ClinVar Variant Classifications

295 submitted variants in ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic3
VUS177
Likely Benign13
Benign8
Conflicting1
50
Pathogenic
3
Likely Pathogenic
177
VUS
13
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
49
0
50
Likely Pathogenic
1
1
1
0
3
VUS
2
169
6
0
177
Likely Benign
0
6
2
5
13
Benign
0
3
2
3
8
Conflicting
1
Total4179608252

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

View in ClinVar →

Protein Context — Lollipop Plot

VWA8 · 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.

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Clinical Literature
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