Is DKC1 p.Ile7Thr (c.20T>C) pathogenic?

DKC1 p.Ile7Thr (c.20T>C) is classified Conflicting classifications of pathogenicity in DKC1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-23). AlphaMissense: likely benign (0.0773); Ultra-rare (popmax 0.0174%, amr); Associated with dyskeratosis congenita.

What condition is associated with DKC1 p.Ile7Thr (c.20T>C)?

DKC1 p.Ile7Thr (c.20T>C) is associated with dyskeratosis congenita (ClinVar).

How common is DKC1 p.Ile7Thr (c.20T>C) in the general population?

DKC1 p.Ile7Thr (c.20T>C) is ultra-rare (popmax 0.0174%, amr) (gnomAD).

How is Dyskeratosis congenita inherited?

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

What do computational predictors say about DKC1 p.Ile7Thr (c.20T>C)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

DKC1 p.Ile7Thr

c.20T>C · rs782343800 · VCV459584

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dyskeratosis congenita

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.429	indeterminate
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP 0.11, phastCons 0.001
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	8.617	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

Grpmax group 0.0174% Admixed American · 8/46,072 alleles

Filtering AF 0.00864% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00627%

Overall 0.000736% 8/1,086,328 alleles · ultra-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
Protein: p.Ile7Thr
Coding: c.20T>C
MANE Select: NM_001363
dbSNP: rs782343800
Type: single nucleotide variant
Location: chrX:154764902 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 7: the '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.Ile7= Likely benign ★ same residue
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

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-ile7thr (accessed [today's date]).

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