Is DKC1 p.Lys504fs (c.1508dup) pathogenic?

DKC1 p.Lys504fs (c.1508dup) is classified Uncertain significance in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Lys504fs (c.1508dup)?

DKC1 p.Lys504fs (c.1508dup) is associated with dyskeratosis congenita (ClinVar).

How is Dyskeratosis congenita inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DKC1 p.Lys504fs

c.1508dup · VCV3626002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.74	GERP 1.8, phastCons 0.98
Region caveats
Repeat context	tandem	(AAG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DKC1
Protein: p.Lys504fs
Coding: c.1508dup
MANE Select: NM_001363
Type: Duplication
Location: chrX:154776828 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 504: the 'disordered' region; the 'nuclear and nucleolar localization' region

Full DKC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dyskeratosis congenita — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dyskeratosis congenita (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

DKC1 p.Lys504_Lys505dup Likely benign ★★ same residue
DKC1 p.Lys504Asn Uncertain significance ★ ⚠ same residue
DKC1 p.Lys504_Lys505del Benign ★ same residue
DKC1 c.1259+7dup Likely benign ★ same condition
DKC1 c.84+15dup Likely benign ★ same condition
DKC1 c.916-15dup Likely benign ★ same condition
DKC1 p.Lys504_Lys505insGlu Benign ★ same residue
DKC1 p.Ala353Val Pathogenic ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dkc1-p-lys504fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown