VWA3A

Chr 16

von Willebrand factor A domain containing 3A

NCBI Gene: 146177 ENSG00000175267 UniProt: A6NCI4 OMIM: 621113

VWA3A encodes a protein predicted to be located in the extracellular region, though its specific function is not well characterized. Mutations cause a rare genetic condition with clinical features documented in GeneReviews, though the inheritance pattern and specific phenotypic details are not provided in the available data. The gene shows tolerance to loss-of-function variants based on constraint metrics.

GeneReviews OMIM ResearchSummary from RefSeq

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

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.92

Clinical Summary— VWA3A

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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

175 VUS of 209 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — VWA3A

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.92LOEUF

pLI 0.000

Z-score 2.11

OE 0.72 (0.57–0.92)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.71Z-score

OE missense 0.92 (0.86–0.98)

581 obs / 631.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.57–0.92)

0≤0.351.4

Missense OE?0.92 (0.86–0.98)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 49 / 67.7Missense obs/exp: 581 / 631.5Syn Z: 2.00

This gene — mechanism propensity

0.6454th %ile

GOF

0.6150th %ile

LOF

0.3843th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

209 submitted variants in ClinVar

ClinVar

Classification Summary

VUS175

Likely Benign14

175

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	175	0	175
Likely Benign	12	2	14
Benign	0	0	0
Total	187	2	189

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

View in ClinVar →

71 pathogenic / likely-pathogenic (of 130) ClinVar copy-number / structural variants overlap VWA3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →