Is DKC1 p.Ile38Thr (c.113T>C) pathogenic?

DKC1 p.Ile38Thr (c.113T>C) is classified Pathogenic in DKC1 (ClinVar, No assertion criteria, 3 submitters; last evaluated 2002-12-01). AlphaMissense: likely pathogenic (0.9647); Absent from gnomAD v4.1; Associated with dyskeratosis congenita, X-linked.

What condition is associated with DKC1 p.Ile38Thr (c.113T>C)?

DKC1 p.Ile38Thr (c.113T>C) is associated with dyskeratosis congenita, X-linked, Hoyeraal-Hreidarsson syndrome (ClinVar).

How common is DKC1 p.Ile38Thr (c.113T>C) in the general population?

DKC1 p.Ile38Thr (c.113T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.Ile38Thr (c.113T>C)?

AlphaMissense predicts likely pathogenic (score 0.9647) — an in-silico prediction, not a clinical call.

DKC1 p.Ile38Thr

c.113T>C · rs28936072 · VCV11593

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9647 · 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	0.9647	likely pathogenic ✓ concordant with ClinVar
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -6.40	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 7.8	GERP 4, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	25.4	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.Ile38Thr
Coding: c.113T>C
MANE Select: NM_001363
dbSNP: rs28936072
Type: single nucleotide variant
Location: chrX:154765472 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 38: a UniProt-annotated variant site (in hhs); an α-helix

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

Also linked: Hoyeraal-Hreidarsson syndrome

Similar variants

DKC1 p.Ile38Met Likely pathogenic ★★ ⚠ same residue
DKC1 p.Ile38Ser Uncertain significance ★ ⚠ same residue
DKC1 p.Ala353Val 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-ile38thr (accessed [today's date]).

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