diff --git a/src/AlternateAllele.php b/src/AlternateAllele.php
new file mode 100644
index 0000000..61da4a8
--- /dev/null
+++ b/src/AlternateAllele.php
@@ -0,0 +1,27 @@
+<?php declare(strict_types=1);
+
+namespace MLL\Utils;
+
+/**
+ * The ALT of a VCF record, where `.` means there is no alternate allele.
+ */
+class AlternateAllele extends DnaSequence
+{
+    public const MISSING = '.';
+
+    public function __construct(string $sequence)
+    {
+        if (trim($sequence) === self::MISSING) {
+            $this->validatedSequence = self::MISSING;
+
+            return;
+        }
+
+        parent::__construct($sequence);
+    }
+
+    public function isMissing(): bool
+    {
+        return $this->validatedSequence === self::MISSING;
+    }
+}
diff --git a/src/DnaSequence.php b/src/DnaSequence.php
index 2d1e063..968f184 100644
--- a/src/DnaSequence.php
+++ b/src/DnaSequence.php
@@ -9,7 +9,7 @@ class DnaSequence
     public function __construct(string $sequence)
     {
         $sequence = trim(strtoupper($sequence));
-        if (\Safe\preg_match('/^[ATGC]*$/', $sequence) === 0) {
+        if (\Safe\preg_match('/^[ATGCN]*$/', $sequence) === 0) {
             throw new \InvalidArgumentException('Invalid DNA sequence');
         }
         $this->validatedSequence = $sequence;
diff --git a/src/VariantIdentifier.php b/src/VariantIdentifier.php
index 5136b49..48f8503 100644
--- a/src/VariantIdentifier.php
+++ b/src/VariantIdentifier.php
@@ -49,7 +49,7 @@ public function toString(VariantIdentifierFormat $format, NamingConvention $nami
 
     private static function parseCanonical(string $value): self
     {
-        if (preg_match('/^(.+)-(\d+)-([ATGC]+)\/([ATGC]+)$/i', $value, $matches) === 0) {
+        if (preg_match('/^(.+)-(\d+)-([ATGCN]+)\/([ATGCN]+|\.)$/i', $value, $matches) === 0) {
             throw new \InvalidArgumentException("Invalid canonical variant identifier format: {$value}.");
         }
 
@@ -58,13 +58,13 @@ private static function parseCanonical(string $value): self
         return new self(
             new GenomicPosition(new Chromosome($matches[1]), NucleotidePosition::fromOneBased(SafeCast::toInt($matches[2]))),
             new DnaSequence($matches[3]),
-            new DnaSequence($matches[4])
+            new AlternateAllele($matches[4])
         );
     }
 
     private static function parseDash(string $value): self
     {
-        if (preg_match('/^(.+)-(\d+)-([ATGC]+)-([ATGC]+)$/i', $value, $matches) === 0) {
+        if (preg_match('/^(.+)-(\d+)-([ATGCN]+)-([ATGCN]+|\.)$/i', $value, $matches) === 0) {
             throw new \InvalidArgumentException("Invalid VCF variant identifier format: {$value}.");
         }
 
@@ -73,7 +73,7 @@ private static function parseDash(string $value): self
         return new self(
             new GenomicPosition(new Chromosome($matches[1]), NucleotidePosition::fromOneBased(SafeCast::toInt($matches[2]))),
             new DnaSequence($matches[3]),
-            new DnaSequence($matches[4])
+            new AlternateAllele($matches[4])
         );
     }
 }
diff --git a/tests/AlternateAlleleTest.php b/tests/AlternateAlleleTest.php
new file mode 100644
index 0000000..946ff6c
--- /dev/null
+++ b/tests/AlternateAlleleTest.php
@@ -0,0 +1,29 @@
+<?php declare(strict_types=1);
+
+namespace MLL\Utils\Tests;
+
+use MLL\Utils\AlternateAllele;
+use PHPUnit\Framework\TestCase;
+
+final class AlternateAlleleTest extends TestCase
+{
+    public function testMissingAllele(): void
+    {
+        $alternateAllele = new AlternateAllele('.');
+        self::assertTrue($alternateAllele->isMissing());
+        self::assertSame('.', $alternateAllele->toString());
+    }
+
+    public function testBases(): void
+    {
+        $alternateAllele = new AlternateAllele('acn');
+        self::assertFalse($alternateAllele->isMissing());
+        self::assertSame('ACN', $alternateAllele->toString());
+    }
+
+    public function testInvalidAlleleThrowsException(): void
+    {
+        $this->expectException(\InvalidArgumentException::class);
+        new AlternateAllele('..');
+    }
+}
diff --git a/tests/DnaSequenceTest.php b/tests/DnaSequenceTest.php
index f145f85..a8e42a2 100644
--- a/tests/DnaSequenceTest.php
+++ b/tests/DnaSequenceTest.php
@@ -56,4 +56,18 @@ public function testLength(): void
         $dnaSequence = new DnaSequence(' GCAT ');
         self::assertSame(4, $dnaSequence->length());
     }
+
+    public function testUnknownBase(): void
+    {
+        $dnaSequence = new DnaSequence('ANGT');
+        self::assertSame('ANGT', $dnaSequence->toString());
+        self::assertSame('TNCA', $dnaSequence->complement());
+        self::assertSame('ACNT', $dnaSequence->reverseComplement());
+    }
+
+    public function testMissingAlleleIsNoDnaSequence(): void
+    {
+        $this->expectException(\InvalidArgumentException::class);
+        new DnaSequence('.');
+    }
 }
diff --git a/tests/VariantIdentifierTest.php b/tests/VariantIdentifierTest.php
index c6e2236..11f2e60 100644
--- a/tests/VariantIdentifierTest.php
+++ b/tests/VariantIdentifierTest.php
@@ -81,6 +81,8 @@ public static function parseVCFProvider(): iterable
         yield 'insertion' => ['chrX-99999-A-ATCG', 'X', 99999, 'A', 'ATCG'];
         yield 'chromosome 22' => ['chr22-100-G-C', '22', 100, 'G', 'C'];
         yield 'mitochondrial' => ['chrM-8000-T-C', 'M', 8000, 'T', 'C'];
+        yield 'unknown base' => ['chr17-42288064-TCAGGC-TGGN', '17', 42288064, 'TCAGGC', 'TGGN'];
+        yield 'missing alternate' => ['chr11-5304332-A-.', '11', 5304332, 'A', '.'];
     }
 
     /** @dataProvider parseCanonicalProvider */
@@ -101,6 +103,8 @@ public static function parseCanonicalProvider(): iterable
         yield 'SNV with chr prefix' => ['chr1-12345-A/T', '1', 12345, 'A', 'T'];
         yield 'multi-base alternate' => ['chr1-12345-A/ATT', '1', 12345, 'A', 'ATT'];
         yield 'without chr prefix' => ['12-500-G/CA', '12', 500, 'G', 'CA'];
+        yield 'unknown base' => ['chr19-13054588-AAGACAAGAA/ANT', '19', 13054588, 'AAGACAAGAA', 'ANT'];
+        yield 'missing alternate' => ['chr11-5304332-A/.', '11', 5304332, 'A', '.'];
     }
 
     public function testParseInvalidVCFThrows(): void
@@ -109,6 +113,12 @@ public function testParseInvalidVCFThrows(): void
         VariantIdentifier::parse('invalid');
     }
 
+    public function testParseMissingReferenceThrows(): void
+    {
+        $this->expectException(\InvalidArgumentException::class);
+        VariantIdentifier::parse('chr11-5304332-.-A');
+    }
+
     public function testParseInvalidCanonicalThrows(): void
     {
         $this->expectException(\InvalidArgumentException::class);