diff --git a/malariagen_data/anoph/cnv_frq.py b/malariagen_data/anoph/cnv_frq.py
index ee4724e20..5ace5751e 100644
--- a/malariagen_data/anoph/cnv_frq.py
+++ b/malariagen_data/anoph/cnv_frq.py
@@ -29,6 +29,32 @@
 from .sample_metadata import _locate_cohorts
 
 
+def _expected_copy_number(contig, sex_contig, df_samples):
+    """Compute expected copy number per sample for a given contig.
+
+    On the sex-linked contig, males are hemizygous (CN=1) and females
+    are diploid (CN=2). On all other contigs, samples are diploid (CN=2).
+
+    If the sex-linked contig is requested but the ``sex_call`` column is
+    missing, a warning is emitted and all samples are treated as diploid
+    rather than silently returning a constant that would misrepresent
+    male hemizygous loci.
+    """
+    if contig != sex_contig:
+        return 2
+    if "sex_call" not in df_samples.columns:
+        warnings.warn(
+            "sex_call column not found; defaulting to diploid (CN=2) for "
+            "all samples on the sex-linked contig. Amplification and "
+            "deletion calls for hemizygous males may be incorrect.",
+            UserWarning,
+            stacklevel=3,
+        )
+        return 2
+    is_male = (df_samples["sex_call"] == "M").values
+    return np.where(is_male, 1, 2)[np.newaxis, :]
+
+
 class AnophelesCnvFrequencyAnalysis(AnophelesCnvData, AnophelesFrequencyAnalysis):
     def __init__(
         self,
@@ -290,11 +316,7 @@ def _gene_cnv_frequencies(
         df_samples = df_samples.set_index("sample_id").loc[sample_id].reset_index()
 
         debug("figure out expected copy number")
-        if region.contig == "X":
-            is_male = (df_samples["sex_call"] == "M").values
-            expected_cn = np.where(is_male, 1, 2)[np.newaxis, :]
-        else:
-            expected_cn = 2
+        expected_cn = _expected_copy_number(region.contig, self._sex_contig, df_samples)
 
         debug(
             "setup output dataframe - two rows for each gene, one for amplification and one for deletion"
@@ -557,11 +579,7 @@ def _gene_cnv_frequencies_advanced(
         )
 
         debug("figure out expected copy number")
-        if region.contig == "X":
-            is_male = (df_samples["sex_call"] == "M").values
-            expected_cn = np.where(is_male, 1, 2)[np.newaxis, :]
-        else:
-            expected_cn = 2
+        expected_cn = _expected_copy_number(region.contig, self._sex_contig, df_samples)
 
         debug("set up intermediates")
         cn = ds_cnv["CN_mode"].values
diff --git a/malariagen_data/anoph/genome_sequence.py b/malariagen_data/anoph/genome_sequence.py
index 3dc380167..981c8ab8a 100644
--- a/malariagen_data/anoph/genome_sequence.py
+++ b/malariagen_data/anoph/genome_sequence.py
@@ -19,7 +19,10 @@ class AnophelesGenomeSequenceData(AnophelesBase):
     _cache_genome: Optional[zarr.hierarchy.Group]
 
     def __init__(
-        self, virtual_contigs: Optional[Mapping[str, Sequence[str]]] = None, **kwargs
+        self,
+        virtual_contigs: Optional[Mapping[str, Sequence[str]]] = None,
+        sex_contig: str = "X",
+        **kwargs,
     ):
         # N.B., this class is designed to work cooperatively, and
         # so it's important that any remaining parameters are passed
@@ -31,6 +34,12 @@ def __init__(
             virtual_contigs = dict()
         self._virtual_contigs = virtual_contigs
 
+        # Store the name of the sex-linked contig. Defaults to "X",
+        # which is correct for all currently supported assemblies, but
+        # can be overridden per species to support assemblies that use
+        # different contig naming conventions.
+        self._sex_contig = sex_contig
+
     @property
     def contigs(self) -> Tuple[str, ...]:
         """Contigs in the reference genome."""
@@ -41,6 +50,11 @@ def virtual_contigs(self) -> Mapping[str, Sequence[str]]:
         """Virtual contigs made by concatenating contigs in the reference genome."""
         return self._virtual_contigs
 
+    @property
+    def sex_contig(self) -> str:
+        """Name of the sex-linked contig used for ploidy-aware analyses."""
+        return self._sex_contig
+
     @property
     def _genome_zarr_path(self) -> str:
         return self.config["GENOME_ZARR_PATH"]
diff --git a/malariagen_data/anopheles.py b/malariagen_data/anopheles.py
index 8342dbb88..9a520286a 100644
--- a/malariagen_data/anopheles.py
+++ b/malariagen_data/anopheles.py
@@ -141,6 +141,7 @@ def __init__(
         taxon_colors: Optional[Mapping[str, str]] = None,
         aim_species_colors: Optional[Mapping[str, str]] = None,
         virtual_contigs: Optional[Mapping[str, Sequence[str]]] = None,
+        sex_contig: str = "X",
         gene_names: Optional[Mapping[str, str]] = None,
         inversion_tag_path: Optional[str] = None,
         unrestricted_use_only: Optional[bool] = None,
@@ -179,6 +180,7 @@ def __init__(
             taxon_colors=taxon_colors,
             aim_species_colors=aim_species_colors,
             virtual_contigs=virtual_contigs,
+            sex_contig=sex_contig,
             gene_names=gene_names,
             inversion_tag_path=inversion_tag_path,
             unrestricted_use_only=unrestricted_use_only,
diff --git a/tests/anoph/test_cnv_frq.py b/tests/anoph/test_cnv_frq.py
index c775ffff0..502bd7d84 100644
--- a/tests/anoph/test_cnv_frq.py
+++ b/tests/anoph/test_cnv_frq.py
@@ -7,7 +7,10 @@
 
 from malariagen_data import af1 as _af1
 from malariagen_data import ag3 as _ag3
-from malariagen_data.anoph.cnv_frq import AnophelesCnvFrequencyAnalysis
+from malariagen_data.anoph.cnv_frq import (
+    AnophelesCnvFrequencyAnalysis,
+    _expected_copy_number,
+)
 from malariagen_data.util import _compare_series_like
 from .test_frq import (
     check_plot_frequencies_heatmap,
@@ -883,3 +886,28 @@ def check_gene_cnv_frequencies_advanced(
             actual_frq = ds["event_frequency"].values[:, cohort_index]
             expect_frq = df_af[f"frq_{cohort_label}"].values
             assert_allclose(actual_frq, expect_frq)
+
+
+def test_expected_copy_number_autosome():
+    df_samples = pd.DataFrame({"sex_call": ["M", "F", "M"]})
+    assert _expected_copy_number("2R", "X", df_samples) == 2
+
+
+def test_expected_copy_number_sex_contig_with_sex_call():
+    df_samples = pd.DataFrame({"sex_call": ["M", "F", "M", "F"]})
+    result = _expected_copy_number("X", "X", df_samples)
+    assert_array_equal(result, np.array([[1, 2, 1, 2]]))
+
+
+def test_expected_copy_number_sex_contig_missing_sex_call():
+    df_samples = pd.DataFrame({"sample_id": ["a", "b", "c"]})
+    with pytest.warns(UserWarning, match="sex_call column not found"):
+        result = _expected_copy_number("X", "X", df_samples)
+    assert result == 2
+
+
+def test_expected_copy_number_custom_sex_contig():
+    df_samples = pd.DataFrame({"sex_call": ["M", "F"]})
+    result = _expected_copy_number("Z", "Z", df_samples)
+    assert_array_equal(result, np.array([[1, 2]]))
+    assert _expected_copy_number("X", "Z", df_samples) == 2
diff --git a/tests/anoph/test_genome_sequence.py b/tests/anoph/test_genome_sequence.py
index a50dcfaac..69d7e39c2 100644
--- a/tests/anoph/test_genome_sequence.py
+++ b/tests/anoph/test_genome_sequence.py
@@ -107,6 +107,25 @@ def test_genome_sequence_region(fixture, api):
         assert seq.shape[0] == stop - start + 1
 
 
+@parametrize_with_cases("fixture,api", cases=".")
+def test_sex_contig_default(fixture, api):
+    assert api.sex_contig == "X"
+
+
+def test_sex_contig_configurable(ag3_sim_fixture):
+    api = AnophelesGenomeSequenceData(
+        url=ag3_sim_fixture.url,
+        public_url=ag3_sim_fixture.url,
+        config_path=_ag3.CONFIG_PATH,
+        major_version_number=_ag3.MAJOR_VERSION_NUMBER,
+        major_version_path=_ag3.MAJOR_VERSION_PATH,
+        pre=True,
+        virtual_contigs=_ag3.VIRTUAL_CONTIGS,
+        sex_contig="Z",
+    )
+    assert api.sex_contig == "Z"
+
+
 def test_virtual_contigs(ag3_sim_api):
     api = ag3_sim_api
     contigs = api.contigs