diff --git a/biology/bcftools/Makefile b/biology/bcftools/Makefile
index 9525d7fd3450..f04c0777bc27 100644
--- a/biology/bcftools/Makefile
+++ b/biology/bcftools/Makefile
@@ -1,61 +1,60 @@
 PORTNAME=	bcftools
-PORTVERSION=	1.17
-PORTREVISION=	1
+PORTVERSION=	1.21
 CATEGORIES=	biology
 
 MAINTAINER=	jwb@FreeBSD.org
 COMMENT=	Tools for manipulating next-generation sequencing data
 WWW=		https://www.htslib.org/
 
 LICENSE=	MIT
 LICENSE_FILE=	${WRKSRC}/LICENSE
 
+BUILD_DEPENDS=	htslib>=1.21:biology/htslib
 LIB_DEPENDS=	libhts.so:biology/htslib
 TEST_DEPENDS=	bash:shells/bash
 RUN_DEPENDS=	bash:shells/bash
 
 USES=		autoreconf gmake localbase perl5 python:env shebangfix
 
 USE_GITHUB=	yes
-USE_PERL5=	test
 
 GH_ACCOUNT=	samtools
 GNU_CONFIGURE=	yes
 GNU_CONFIGURE_MANPREFIX=	${PREFIX}/share
 SHEBANG_FILES=	misc/* test/test.pl
 
 OPTIONS_DEFINE=		GPL
 GPL_DESC=		Enable modules that rely on GPL code
 OPTIONS_DEFAULT=	GPL
 
 GPL_LIB_DEPENDS=	libgsl.so:math/gsl
 
 .include <bsd.port.options.mk>
 
 .if ${PORT_OPTIONS:MGPL}
 MAKE_ENV+=	USE_GPL=1
 LICENSE+=	GPLv3
 LICENSE_COMB=	multi
 .endif
 
 TEST_TARGET=	test
 
 pre-configure:
 	@${REINPLACE_CMD} -e 's|@PORTVERSION@|${PORTVERSION}|g' \
 		${WRKSRC}/configure.ac
 
 post-install:
 	${MV} ${STAGEDIR}${PREFIX}/bin/color-chrs.pl \
 		${STAGEDIR}${PREFIX}/bin/color-chrs
 	${MV} ${STAGEDIR}${PREFIX}/bin/guess-ploidy.py\
 	       ${STAGEDIR}${PREFIX}/bin/guess-ploidy
 	${MV} /${STAGEDIR}${PREFIX}/bin/plot-roh.py \
 		${STAGEDIR}${PREFIX}/bin/plot-roh
 	${MV} ${STAGEDIR}${PREFIX}/bin/run-roh.pl \
 		${STAGEDIR}${PREFIX}/bin/run-roh
 	${MV} ${STAGEDIR}${PREFIX}/bin/vcfutils.pl \
 		${STAGEDIR}${PREFIX}/bin/vcfutils
 	${MV} ${STAGEDIR}${PREFIX}/bin/plot-vcfstats \
 		${STAGEDIR}${PREFIX}/bin/
 
 .include <bsd.port.mk>
diff --git a/biology/bcftools/distinfo b/biology/bcftools/distinfo
index e485c96d9038..a39dbc0e3ca0 100644
--- a/biology/bcftools/distinfo
+++ b/biology/bcftools/distinfo
@@ -1,3 +1,3 @@
-TIMESTAMP = 1677246068
-SHA256 (samtools-bcftools-1.17_GH0.tar.gz) = e6fdb4c94b531671ea8a0b00cb9245aa2602f6c4480621e45dac76338f590b9e
-SIZE (samtools-bcftools-1.17_GH0.tar.gz) = 3481344
+TIMESTAMP = 1727437561
+SHA256 (samtools-bcftools-1.21_GH0.tar.gz) = 7484695c5d833fb1a89c2b886ec302db0514ba3c8e5ef7397b9302fa8bd37f8d
+SIZE (samtools-bcftools-1.21_GH0.tar.gz) = 3665160
diff --git a/biology/bcftools/files/patch-Makefile b/biology/bcftools/files/patch-Makefile
index 3299954ae45b..a00ca91d18cb 100644
--- a/biology/bcftools/files/patch-Makefile
+++ b/biology/bcftools/files/patch-Makefile
@@ -1,33 +1,32 @@
---- Makefile.orig	2021-03-17 09:16:18 UTC
+--- Makefile.orig	2024-09-27 11:44:03 UTC
 +++ Makefile
-@@ -58,13 +58,14 @@ pluginpath  = $(plugindir)
+@@ -59,13 +59,13 @@ misc_bindir = $(bindir)
  # Installation location for $(MISC_PROGRAMS) and $(MISC_SCRIPTS)
  misc_bindir = $(bindir)
  
 -MKDIR_P = mkdir -p
 -INSTALL = install -p
 -INSTALL_DATA    = $(INSTALL) -m 644
 -INSTALL_DIR     = $(MKDIR_P) -m 755
 -INSTALL_MAN     = $(INSTALL_DATA)
 -INSTALL_PROGRAM = $(INSTALL)
 -INSTALL_SCRIPT  = $(INSTALL_PROGRAM)
-+# Use BSD_INSTALL_PROGRAM to strip when WITH_DEBUG not set
-+MKDIR_P 	= mkdir -p
-+INSTALL 	= install -p
-+INSTALL_DATA    = ${BSD_INSTALL_DATA}
-+INSTALL_DIR     = $(MKDIR_P)
-+INSTALL_MAN     = ${BSD_INSTALL_MAN}
-+INSTALL_PROGRAM = ${BSD_INSTALL_PROGRAM}
-+INSTALL_SCRIPT  = ${BSD_INSTALL_SCRIPT}
++MKDIR_P		= mkdir -p
++INSTALL		= install -p
++INSTALL_DATA	= ${BSD_INSTALL_DATA}
++INSTALL_DIR	= $(MKDIR_P)
++INSTALL_MAN	= ${BSD_INSTALL_MAN}
++INSTALL_PROGRAM	= ${BSD_INSTALL_PROGRAM}
++INSTALL_SCRIPT	= ${BSD_INSTALL_SCRIPT}
  
  PROGRAMS = bcftools
  MISC_SCRIPTS = \
-@@ -142,7 +143,7 @@ print-version:
- ifdef USE_GPL
+@@ -144,7 +144,7 @@ ifdef USE_GPL
      main.o : EXTRA_CPPFLAGS += -DUSE_GPL
      OBJS += polysomy.o peakfit.o
--    GSL_LIBS ?= -lgsl -lcblas
-+    GSL_LIBS ?= -lgslcblas
+     ifndef GSL_LIBS
+-        GSL_LIBS += -lgsl -lcblas
++        GSL_LIBS += -lgslcblas
+     endif
  endif
  
- print-%:
diff --git a/biology/bcftools/pkg-plist b/biology/bcftools/pkg-plist
index 6f40c8532f31..6aa7a6d9f73e 100644
--- a/biology/bcftools/pkg-plist
+++ b/biology/bcftools/pkg-plist
@@ -1,49 +1,48 @@
 bin/bcftools
 bin/color-chrs
 bin/gff2gff.py
 bin/guess-ploidy
 bin/plot-roh
 bin/plot-vcfstats
 bin/run-roh
 bin/vcfutils
 libexec/bcftools/GTisec.so
 libexec/bcftools/GTsubset.so
 libexec/bcftools/ad-bias.so
 libexec/bcftools/add-variantkey.so
 libexec/bcftools/af-dist.so
 libexec/bcftools/allele-length.so
 libexec/bcftools/check-ploidy.so
 libexec/bcftools/check-sparsity.so
 libexec/bcftools/color-chrs.so
 libexec/bcftools/contrast.so
 libexec/bcftools/counts.so
 libexec/bcftools/dosage.so
 libexec/bcftools/fill-AN-AC.so
 libexec/bcftools/fill-from-fasta.so
 libexec/bcftools/fill-tags.so
 libexec/bcftools/fixploidy.so
 libexec/bcftools/fixref.so
 libexec/bcftools/frameshifts.so
 libexec/bcftools/guess-ploidy.so
 libexec/bcftools/gvcfz.so
 libexec/bcftools/impute-info.so
 libexec/bcftools/indel-stats.so
 libexec/bcftools/isecGT.so
-libexec/bcftools/mendelian.so
 libexec/bcftools/mendelian2.so
 libexec/bcftools/missing2ref.so
 libexec/bcftools/parental-origin.so
 libexec/bcftools/prune.so
 libexec/bcftools/remove-overlaps.so
 libexec/bcftools/scatter.so
 libexec/bcftools/setGT.so
 libexec/bcftools/smpl-stats.so
 libexec/bcftools/split-vep.so
 libexec/bcftools/split.so
 libexec/bcftools/tag2tag.so
 libexec/bcftools/trio-dnm2.so
 libexec/bcftools/trio-stats.so
 libexec/bcftools/trio-switch-rate.so
 libexec/bcftools/variant-distance.so
 libexec/bcftools/variantkey-hex.so
 share/man/man1/bcftools.1.gz