Is DKC1 p.Asn63Lys (c.189T>G) pathogenic?

DKC1 p.Asn63Lys (c.189T>G) is classified Pathogenic/Likely pathogenic in DKC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-23). AlphaMissense: likely pathogenic (0.8704); Absent from gnomAD v4.1; Associated with DKC1-Related Disorders.

What condition is associated with DKC1 p.Asn63Lys (c.189T>G)?

DKC1 p.Asn63Lys (c.189T>G) is associated with DKC1-Related Disorders, dyskeratosis congenita (ClinVar).

How common is DKC1 p.Asn63Lys (c.189T>G) in the general population?

DKC1 p.Asn63Lys (c.189T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.Asn63Lys (c.189T>G)?

AlphaMissense predicts likely pathogenic (score 0.8704) — an in-silico prediction, not a clinical call.

DKC1 p.Asn63Lys

c.189T>G · rs2523680394 · VCV1782258

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8704 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DKC1-Related Disorders

Computational evidence

Protein change
AlphaMissense	0.8704	likely pathogenic ✓ concordant with ClinVar
REVEL	0.705	pathogenic-leaning
SaProt	LLR -5.44	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.011	GERP 1.6, phastCons 0.94
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	22.5	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.Asn63Lys
Coding: c.189T>G
MANE Select: NM_001363
dbSNP: rs2523680394
Type: single nucleotide variant
Location: chrX:154765924 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 63: a β-strand

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

Disease context

Also linked: dyskeratosis congenita

Similar variants

DKC1 p.Asn63= Likely benign ★ same residue
DKC1 p.Ala353Val 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-p-asn63lys (accessed [today's date]).

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