Is DKC1 p.His68Gln (c.204C>G) pathogenic?

DKC1 p.His68Gln (c.204C>G) is classified Likely pathogenic in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). AlphaMissense: likely pathogenic (0.9514); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, X-linked.

What condition is associated with DKC1 p.His68Gln (c.204C>G)?

DKC1 p.His68Gln (c.204C>G) is associated with dyskeratosis congenita, X-linked (ClinVar).

How common is DKC1 p.His68Gln (c.204C>G) in the general population?

DKC1 p.His68Gln (c.204C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.His68Gln (c.204C>G)?

AlphaMissense predicts likely pathogenic (score 0.9514) — an in-silico prediction, not a clinical call.

DKC1 p.His68Gln

c.204C>G · rs199422245 · VCV1343818

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9514 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita, X-linked

Computational evidence

Protein change
AlphaMissense	0.9514	likely pathogenic ✓ concordant with ClinVar
REVEL	0.792	moderately pathogenic-leaning
SaProt	LLR -8.67	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 0.58	GERP 0.91, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	21.3	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.His68Gln
Coding: c.204C>G
MANE Select: NM_001363
dbSNP: rs199422245
Type: single nucleotide variant
Location: chrX:154765939 (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, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DKC1 p.His68Arg Pathogenic ★ same residue
DKC1 p.Ala353Val Pathogenic ★★ ⚠ same condition
DKC1 p.Ile38Met Likely pathogenic ★★ ⚠ same condition
DKC1 p.Thr49Met Pathogenic ★★ ⚠ same condition
DKC1 p.Thr66Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
DKC1 p.Gln414Glu Uncertain significance ★★ ⚠ same condition
DKC1 p.Glu440Lys Uncertain significance ★★ ⚠ same condition
DKC1 p.Ile163Leu 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-his68gln (accessed [today's date]).

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