ACRV1

Chr 11

acrosomal vesicle protein 1

Also known as: D11S4365, SP-10, SPACA2

The protein is a testis-specific acrosomal vesicle component that functions in sperm-zona binding or penetration during fertilization. Mutations in this gene cause globozoospermia, a form of male infertility characterized by round-headed sperm lacking acrosomes, and follows autosomal recessive inheritance. This gene shows very low constraint against loss-of-function variants in the general population.

Summary from RefSeq
Research Assistant →
0
Active trials
3
Pubs (1 yr)
62
P/LP submissions
0%
P/LP missense
1.43
LOEUF
DN
Mechanism· predicted
Clinical SummaryACRV1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 unique Pathogenic / Likely Pathogenic· 28 VUS of 93 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.43LOEUF
pLI 0.000
Z-score 0.50
OE 0.84 (0.521.43)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.89Z-score
OE missense 0.79 (0.670.92)
110 obs / 139.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.84 (0.521.43)
00.351.4
Missense OE0.79 (0.670.92)
00.61.4
Synonymous OE1.17
01.21.6
LoF obs/exp: 10 / 11.8Missense obs/exp: 110 / 139.7Syn Z: -0.96
DN
0.6840th %ile
GOF
0.5563th %ile
LOF
0.3356th %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

93 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic2
VUS28
Likely Benign1
60
Pathogenic
2
Likely Pathogenic
28
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
60
0
60
Likely Pathogenic
0
0
2
0
2
VUS
0
24
4
0
28
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total02466191

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

View in ClinVar →

Protein Context — Lollipop Plot

ACRV1 · protein map & ClinVar variants

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

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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