diff --git a/gnomad/sample_qc/pipeline.py b/gnomad/sample_qc/pipeline.py
index 31bc0992e..362b7a53d 100644
--- a/gnomad/sample_qc/pipeline.py
+++ b/gnomad/sample_qc/pipeline.py
@@ -11,7 +11,7 @@
 from gnomad.utils.reference_genome import get_reference_genome
 from gnomad.utils.sparse_mt import impute_sex_ploidy
 
-from typing import List, Optional
+from typing import List, Optional, Union
 
 logging.basicConfig(format="%(levelname)s (%(name)s %(lineno)s): %(message)s")
 logger = logging.getLogger(__name__)
@@ -209,7 +209,7 @@ def get_qc_mt(
 
 
 def annotate_sex(
-    mt: hl.MatrixTable,
+    mtds: Union[hl.MatrixTable, hl.vds.VariantDataset],
     is_sparse: bool = True,
     excluded_intervals: Optional[hl.Table] = None,
     included_intervals: Optional[hl.Table] = None,
@@ -225,7 +225,7 @@ def annotate_sex(
 
     Return Table with the following fields:
         - s (str): Sample
-        - chr20_mean_dp (float32): Sample's mean coverage over chromosome 20.
+        - `normalization_contig`_mean_dp (float32): Sample's mean coverage over the specified `normalization_contig`.
         - chrX_mean_dp (float32): Sample's mean coverage over chromosome X.
         - chrY_mean_dp (float32): Sample's mean coverage over chromosome Y.
         - chrX_ploidy (float32): Sample's imputed ploidy over chromosome X.
@@ -238,7 +238,7 @@ def annotate_sex(
         - Y_karyotype (str): Sample's chromosome Y karyotype.
         - sex_karyotype (str): Sample's sex karyotype.
 
-    :param mt: Input MatrixTable
+    :param mtds: Input MatrixTable or VariantDataset
     :param bool is_sparse: Whether input MatrixTable is in sparse data format
     :param excluded_intervals: Optional table of intervals to exclude from the computation.
     :param included_intervals: Optional table of intervals to use in the computation. REQUIRED for exomes.
@@ -252,14 +252,38 @@ def annotate_sex(
     :return: Table of samples and their imputed sex karyotypes.
     """
     logger.info("Imputing sex chromosome ploidies...")
-    if is_sparse:
-        ploidy_ht = impute_sex_ploidy(
-            mt, excluded_intervals, included_intervals, normalization_contig
+
+    is_vds = isinstance(mtds, hl.vds.VariantDataset)
+    if is_vds:
+        if excluded_intervals is not None:
+            raise NotImplementedError(
+                "The use of the parameter 'excluded_intervals' is currently not implemented for imputing sex chromosome ploidy on a VDS!"
+            )
+        ploidy_ht = hl.vds.impute_sex_chromosome_ploidy(
+            mtds,
+            calling_intervals=included_intervals,
+            normalization_contig=normalization_contig,
         )
-    else:
-        raise NotImplementedError(
-            "Imputing sex ploidy does not exist yet for dense data."
+        ploidy_ht = ploidy_ht.rename(
+            {
+                "x_ploidy": "chrX_ploidy",
+                "y_ploidy": "chrY_ploidy",
+                "x_mean_dp": "chrX_mean_dp",
+                "y_mean_dp": "chrY_mean_dp",
+                "autosomal_mean_dp": f"{normalization_contig}_mean_dp",
+            }
         )
+        mt = mtds.variant_data
+    else:
+        mt = mtds
+        if is_sparse:
+            ploidy_ht = impute_sex_ploidy(
+                mt, excluded_intervals, included_intervals, normalization_contig
+            )
+        else:
+            raise NotImplementedError(
+                "Imputing sex ploidy does not exist yet for dense data."
+            )
 
     x_contigs = get_reference_genome(mt.locus).x_contigs
     logger.info("Filtering mt to biallelic SNPs in X contigs: %s", x_contigs)
@@ -269,8 +293,15 @@ def annotate_sex(
         mt = mt.filter_rows(
             (hl.len(mt.alleles) == 2) & hl.is_snp(mt.alleles[0], mt.alleles[1])
         )
+
+    build = get_reference_genome(mt.locus).name
     mt = hl.filter_intervals(
-        mt, [hl.parse_locus_interval(contig) for contig in x_contigs]
+        mt,
+        [
+            hl.parse_locus_interval(contig, reference_genome=build)
+            for contig in x_contigs
+        ],
+        keep=True,
     )
 
     if sites_ht is not None:
diff --git a/gnomad/utils/file_utils.py b/gnomad/utils/file_utils.py
index a40a18b1e..988cf5090 100644
--- a/gnomad/utils/file_utils.py
+++ b/gnomad/utils/file_utils.py
@@ -11,7 +11,8 @@
 from typing import Callable, List, Dict, Optional, Tuple, Union
 
 import hail as hl
-from hailtop.aiotools import LocalAsyncFS, RouterAsyncFS, AsyncFS
+from hailtop.aiotools import LocalAsyncFS, AsyncFS
+from hailtop.aiotools.router_fs import RouterAsyncFS
 from hailtop.aiogoogle import GoogleStorageAsyncFS
 from hailtop.utils import bounded_gather, tqdm