Is DKC1 p.Lys504Asn (c.1512G>T) pathogenic?

DKC1 p.Lys504Asn (c.1512G>T) is classified Uncertain significance in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). AlphaMissense: ambiguous (0.4915); Absent from gnomAD v4.1; Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Lys504Asn (c.1512G>T)?

DKC1 p.Lys504Asn (c.1512G>T) is associated with dyskeratosis congenita (ClinVar).

How common is DKC1 p.Lys504Asn (c.1512G>T) in the general population?

DKC1 p.Lys504Asn (c.1512G>T) is absent from gnomAD v4.1 (gnomAD).

How is Dyskeratosis congenita inherited?

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

What do computational predictors say about DKC1 p.Lys504Asn (c.1512G>T)?

AlphaMissense predicts ambiguous (score 0.4915) — an in-silico prediction, not a clinical call.

DKC1 p.Lys504Asn

c.1512G>T · rs1557265783 · VCV529180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4915 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.4915	ambiguous
REVEL	0.445	indeterminate
SaProt	LLR -10.92	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 3.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 1,637 bp · p 0.19 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DKC1
Protein: p.Lys504Asn
Coding: c.1512G>T
MANE Select: NM_001363
dbSNP: rs1557265783
Type: single nucleotide variant
Location: chrX:154776834 (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.Lys504fs Uncertain significance ★ same residue
DKC1 p.Lys504_Lys505del Benign ★ same residue
DKC1 p.Ala353Val Pathogenic ★★ ⚠ same condition
DKC1 p.Asn63Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
DKC1 p.Thr49Met Pathogenic ★★ ⚠ same condition
DKC1 p.Thr66Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
DKC1 c.1339-10T>G Uncertain significance ★★ 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-lys504asn (accessed [today's date]).

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