diff --git a/CHANGELOG.md b/CHANGELOG.md
index 2db8af46..c2e58fd5 100644
--- a/CHANGELOG.md
+++ b/CHANGELOG.md
@@ -18,6 +18,7 @@ and this project adheres to [Semantic Versioning](https://semver.org/spec/v2.0.0
 
 ### `Changed`
 
+- Refactored code to only handle clinical variants in the generate_clinical_set workflow [#693](https://github.com/nf-core/raredisease/pull/693)
 - Updated `add_most_severe_consequence` and `add_most_severe_pli` to fix spelling and language server warnings [#689](https://github.com/nf-core/raredisease/pull/689)
 - Refactored code to address issues highlighted by language server [#688](https://github.com/nf-core/raredisease/pull/688)
 - Changed for loop to each in create_pedigree_file [#683](https://github.com/nf-core/raredisease/pull/683)
diff --git a/subworkflows/local/annotate_mobile_elements.nf b/subworkflows/local/annotate_mobile_elements.nf
index cfd66de9..2d08ca07 100644
--- a/subworkflows/local/annotate_mobile_elements.nf
+++ b/subworkflows/local/annotate_mobile_elements.nf
@@ -78,6 +78,6 @@ workflow ANNOTATE_MOBILE_ELEMENTS {
         ch_versions = ch_versions.mix( BCFTOOLS_VIEW_FILTER.out.versions )
 
     emit:
-        vcf      = BCFTOOLS_VIEW_FILTER.out.vcf     // channel: [ val(meta), path(vcf) ]
+        vcf_ann  = BCFTOOLS_VIEW_FILTER.out.vcf     // channel: [ val(meta), path(vcf) ]
         versions = ch_versions                      // channel: [ path(versions.yml) ]
 }
diff --git a/subworkflows/local/annotate_mt_snvs.nf b/subworkflows/local/annotate_mt_snvs.nf
index 306d8ed0..b1fba8b0 100644
--- a/subworkflows/local/annotate_mt_snvs.nf
+++ b/subworkflows/local/annotate_mt_snvs.nf
@@ -31,7 +31,6 @@ workflow ANNOTATE_MT_SNVS {
     main:
         ch_versions     = Channel.empty()
         ch_haplog       = Channel.empty()
-        ch_haplogrep_in = Channel.empty()
 
         // add prefix to meta
         ch_mt_vcf
diff --git a/subworkflows/local/generate_clinical_set.nf b/subworkflows/local/generate_clinical_set.nf
index 8fb541af..3ed94ad6 100644
--- a/subworkflows/local/generate_clinical_set.nf
+++ b/subworkflows/local/generate_clinical_set.nf
@@ -4,7 +4,6 @@
 
 include { ENSEMBLVEP_FILTERVEP } from '../../modules/nf-core/ensemblvep/filtervep'
 include { TABIX_BGZIP          } from '../../modules/nf-core/tabix/bgzip'
-include { TABIX_TABIX          } from '../../modules/nf-core/tabix/tabix'
 include { BCFTOOLS_FILTER      } from '../../modules/nf-core/bcftools/filter'
 
 workflow GENERATE_CLINICAL_SET {
@@ -16,15 +15,8 @@ workflow GENERATE_CLINICAL_SET {
     main:
         ch_versions = Channel.empty()
 
-        ch_vcf
-            .multiMap { meta, vcf ->
-                clinical: [ meta + [ set: "clinical" ], vcf ]
-                research: [ meta + [ set: "research" ], vcf ]
-            }
-            .set { ch_clin_research_vcf }
-
         ENSEMBLVEP_FILTERVEP(
-            ch_clin_research_vcf.clinical,
+            ch_vcf,
             ch_hgnc_ids
         )
         .output
@@ -40,17 +32,9 @@ workflow GENERATE_CLINICAL_SET {
             ch_versions = ch_versions.mix( TABIX_BGZIP.out.versions )
         }
 
-        ch_clin_research_vcf.research
-            .mix( ch_clinical )
-            .set { ch_clin_research_split }
-
-        TABIX_TABIX( ch_clin_research_split )
-
         ch_versions = ch_versions.mix( ENSEMBLVEP_FILTERVEP.out.versions )
-        ch_versions = ch_versions.mix( TABIX_TABIX.out.versions )
 
     emit:
-        vcf      = ch_clin_research_split // channel: [ val(meta), path(vcf) ]
-        tbi      = TABIX_TABIX.out.tbi    // channel: [ val(meta), path(tbi) ]
-        versions = ch_versions            // channel: [ path(versions.yml) ]
+        vcf      = ch_clinical // channel: [ val(meta), path(vcf) ]
+        versions = ch_versions // channel: [ path(versions.yml) ]
 }
diff --git a/workflows/raredisease.nf b/workflows/raredisease.nf
index e03021b2..ad905885 100644
--- a/workflows/raredisease.nf
+++ b/workflows/raredisease.nf
@@ -496,15 +496,23 @@ workflow RAREDISEASE {
             ).set { ch_snv_annotate }
             ch_versions = ch_versions.mix(ch_snv_annotate.versions)
 
+            ch_snv_annotate.vcf_ann
+                .multiMap { meta, vcf ->
+                    clinical: [ meta + [ set: "clinical" ], vcf ]
+                    research: [ meta + [ set: "research" ], vcf ]
+                }
+                .set { ch_clin_research_snv_vcf }
+
             GENERATE_CLINICAL_SET_SNV(
-                ch_snv_annotate.vcf_ann,
+                ch_clin_research_snv_vcf.clinical,
                 ch_hgnc_ids,
                 false
             )
             ch_versions = ch_versions.mix(GENERATE_CLINICAL_SET_SNV.out.versions)
 
+            ch_ann_csq_snv_in = GENERATE_CLINICAL_SET_SNV.out.vcf.mix(ch_clin_research_snv_vcf.research)
             ANN_CSQ_PLI_SNV (
-                GENERATE_CLINICAL_SET_SNV.out.vcf,
+                ch_ann_csq_snv_in,
                 ch_variant_consequences_snv
             )
             ch_versions = ch_versions.mix(ANN_CSQ_PLI_SNV.out.versions)
@@ -549,15 +557,23 @@ workflow RAREDISEASE {
             ).set { ch_mt_annotate }
             ch_versions = ch_versions.mix(ch_mt_annotate.versions)
 
+            ch_mt_annotate.vcf_ann
+                .multiMap { meta, vcf ->
+                    clinical: [ meta + [ set: "clinical" ], vcf ]
+                    research: [ meta + [ set: "research" ], vcf ]
+                }
+                .set { ch_clin_research_mt_vcf }
+
             GENERATE_CLINICAL_SET_MT(
-                ch_mt_annotate.vcf_ann,
+                ch_clin_research_mt_vcf.clinical,
                 ch_hgnc_ids,
                 true
             )
             ch_versions = ch_versions.mix(GENERATE_CLINICAL_SET_MT.out.versions)
 
+            ch_ann_csq_mtsnv_in = GENERATE_CLINICAL_SET_MT.out.vcf.mix(ch_clin_research_mt_vcf.research)
             ANN_CSQ_PLI_MT(
-                GENERATE_CLINICAL_SET_MT.out.vcf,
+                ch_ann_csq_mtsnv_in,
                 ch_variant_consequences_snv
             )
             ch_versions = ch_versions.mix(ANN_CSQ_PLI_MT.out.versions)
@@ -625,15 +641,24 @@ workflow RAREDISEASE {
             ).set { ch_sv_annotate }
             ch_versions = ch_versions.mix(ch_sv_annotate.versions)
 
+            ch_sv_annotate.vcf_ann
+                .multiMap { meta, vcf ->
+                    clinical: [ meta + [ set: "clinical" ], vcf ]
+                    research: [ meta + [ set: "research" ], vcf ]
+                }
+                .set { ch_clin_research_sv_vcf }
+
             GENERATE_CLINICAL_SET_SV(
-                ch_sv_annotate.vcf_ann,
+                ch_clin_research_sv_vcf.clinical,
                 ch_hgnc_ids,
                 false
             )
             ch_versions = ch_versions.mix(GENERATE_CLINICAL_SET_SV.out.versions)
 
+            ch_ann_csq_sv_in = GENERATE_CLINICAL_SET_SV.out.vcf.mix(ch_clin_research_sv_vcf.research)
+
             ANN_CSQ_PLI_SV (
-                GENERATE_CLINICAL_SET_SV.out.vcf,
+                ch_ann_csq_sv_in,
                 ch_variant_consequences_sv
             )
             ch_versions = ch_versions.mix(ANN_CSQ_PLI_SV.out.versions)
@@ -684,16 +709,25 @@ workflow RAREDISEASE {
                 params.genome,
                 params.vep_cache_version,
                 ch_vep_extra_files
-            )
+            ).set { ch_me_annotate }
             ch_versions = ch_versions.mix(ANNOTATE_MOBILE_ELEMENTS.out.versions)
 
+            ch_me_annotate.vcf_ann
+                .multiMap { meta, vcf ->
+                    clinical: [ meta + [ set: "clinical" ], vcf ]
+                    research: [ meta + [ set: "research" ], vcf ]
+                }
+                .set { ch_clin_research_me_vcf }
+
             GENERATE_CLINICAL_SET_ME(
-                ANNOTATE_MOBILE_ELEMENTS.out.vcf,
+                ch_clin_research_me_vcf.clinical,
                 ch_hgnc_ids,
                 false
             )
             ch_versions = ch_versions.mix( GENERATE_CLINICAL_SET_ME.out.versions )
 
+            ch_ann_csq_me_in = GENERATE_CLINICAL_SET_ME.out.vcf.mix(ch_clin_research_me_vcf.research)
+
             ANN_CSQ_PLI_ME(
                 GENERATE_CLINICAL_SET_ME.out.vcf,
                 ch_variant_consequences_sv