Is DKC1 p.Lys472del (c.1409AGA[2]) pathogenic?

DKC1 p.Lys472del (c.1409AGA[2]) is classified Benign/Likely benign in DKC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-24). Ultra-rare (popmax 0.0105%, afr); Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Lys472del (c.1409AGA[2])?

DKC1 p.Lys472del (c.1409AGA[2]) is associated with dyskeratosis congenita (ClinVar).

How common is DKC1 p.Lys472del (c.1409AGA[2]) in the general population?

DKC1 p.Lys472del (c.1409AGA[2]) is ultra-rare (popmax 0.0105%, afr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

DKC1 p.Lys472del

c.1409AGA[2] · rs781922569 · VCV569599

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0105%, afr)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.6	GERP -1.2
Overall
CADD	17.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0105% African / African-American · 6/57,349 alleles

Filtering AF 0.00455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00306%

Overall 0.00231% 28/1,210,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0105%	9,558
Ashkenazi Jewishnot grpmax-eligible	0.00908%	11,017
Remaining individualsnot grpmax-eligible	0.00841%	11,894
Admixed American	0.00654%	15,289
South Asian	0.00176%	56,772
European (non-Finnish)	0.00134%	74,590

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DKC1
Protein: p.Lys472del
Coding: c.1409AGA[2]
MANE Select: NM_001363
dbSNP: rs781922569
Type: Microsatellite
Location: chrX:154776256 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 472: 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.Lys472= Likely benign ★ same residue
DKC1 p.Lys504_Lys505dup Likely benign ★★ same condition
DKC1 p.Lys505dup Benign/Likely benign ★★ same condition
DKC1 c.1036+6_1036+7del Uncertain significance ★ same condition
DKC1 p.Lys17del Conflicting classifications of pathogenicity ★ same condition
DKC1 p.Lys503_Lys505del Uncertain significance ★ same condition
DKC1 p.Lys505del Conflicting classifications of pathogenicity ★ same condition
DKC1 c.17-14_17-13del Likely benign ★ 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-lys472del (accessed [today's date]).

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