Is DKC1 p.Thr66Ile (c.197C>T) pathogenic?

DKC1 p.Thr66Ile (c.197C>T) is classified Likely pathogenic in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). AlphaMissense: likely pathogenic (0.972); Absent from gnomAD v4.1.

How common is DKC1 p.Thr66Ile (c.197C>T) in the general population?

DKC1 p.Thr66Ile (c.197C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.Thr66Ile (c.197C>T)?

AlphaMissense predicts likely pathogenic (score 0.972) — an in-silico prediction, not a clinical call.

DKC1 p.Thr66Ile

c.197C>T · rs2523680452 · VCV2579111

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.972	likely pathogenic ✓ concordant with ClinVar
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -12.70	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 7.6	GERP 3.9, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	26.3	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.Thr66Ile
Coding: c.197C>T
MANE Select: NM_001363
dbSNP: rs2523680452
Type: single nucleotide variant
Location: chrX:154765932 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB
Residue 66: a UniProt-annotated variant site (in dkcx; decreases interaction with shq1)

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

Similar variants

DKC1 p.Thr66Ala Pathogenic/Likely pathogenic ★★ ⚠ same residue
DKC1 p.Ala353Val Pathogenic ★★ ⚠ same type
DKC1 p.Asn63Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
DKC1 p.Ile38Met Likely pathogenic ★★ ⚠ same type
DKC1 p.Thr49Met Pathogenic ★★ ⚠ same type
DKC1 c.1339-10T>G Uncertain significance ★★ same type
DKC1 c.16+5G>A Uncertain significance ★★ same type
DKC1 c.640+3G>A Uncertain significance ★★ same type

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-thr66ile (accessed [today's date]).

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