Is DKC1 c.263+16A>G pathogenic?

DKC1 c.263+16A>G is classified Likely benign in DKC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-17). Very rare (popmax 0.0019%, nfe); Associated with dyskeratosis congenita.

What condition is associated with DKC1 c.263+16A>G?

DKC1 c.263+16A>G is associated with dyskeratosis congenita (ClinVar).

How common is DKC1 c.263+16A>G in the general population?

DKC1 c.263+16A>G is very rare (popmax 0.0019%, nfe) (gnomAD).

How is Dyskeratosis congenita inherited?

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

DKC1 c.263+16A>G

rs782490890 · VCV1566170

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0019%, nfe)

Conditions

dyskeratosis congenita

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +16	near-intronic (+16 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -1.8
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	0.996	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0019% European (non-Finnish) · 16/841,244 alleles

Filtering AF 0.00113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000911%

Overall 0.00139% 16/1,151,117 alleles · very rare

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
Coding: c.263+16A>G
MANE Select: NM_001363
dbSNP: rs782490890
Type: single nucleotide variant
Location: chrX:154766014 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB

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.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
DKC1 c.16+5G>A Uncertain significance ★★ same condition
DKC1 c.640+3G>A Uncertain significance ★★ same condition
DKC1 p.Ala162Thr 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-c-263-plus-16a-g (accessed [today's date]).

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