Is DKC1 p.Asp374Asn (c.1120G>A) pathogenic?

DKC1 p.Asp374Asn (c.1120G>A) is classified Uncertain significance in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: likely pathogenic (0.8328); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, X-linked.

What condition is associated with DKC1 p.Asp374Asn (c.1120G>A)?

DKC1 p.Asp374Asn (c.1120G>A) is associated with dyskeratosis congenita, X-linked (ClinVar).

How common is DKC1 p.Asp374Asn (c.1120G>A) in the general population?

DKC1 p.Asp374Asn (c.1120G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.Asp374Asn (c.1120G>A)?

AlphaMissense predicts likely pathogenic (score 0.8328) — an in-silico prediction, not a clinical call.

DKC1 p.Asp374Asn

c.1120G>A · rs2523700189 · VCV3255134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8328 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dyskeratosis congenita, X-linked

Computational evidence

Protein change
AlphaMissense	0.8328	likely pathogenic
REVEL	0.712	pathogenic-leaning
SaProt	LLR -10.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 3.9, phastCons 1
Regional constraint	o/e 0.29	constrained · MANE · 8,165 bp · p 2.1e-24 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Asp374Asn
Coding: c.1120G>A
MANE Select: NM_001363
dbSNP: rs2523700189
Type: single nucleotide variant
Location: chrX:154773214 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 374: a β-strand

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.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
DKC1 p.Ile187Leu 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-asp374asn (accessed [today's date]).

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