Is DKC1 p.Pro97Thr (c.289C>A) pathogenic?

DKC1 p.Pro97Thr (c.289C>A) is classified Uncertain significance in DKC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-18). AlphaMissense: likely pathogenic (0.9546); Absent from gnomAD v4.1.

How common is DKC1 p.Pro97Thr (c.289C>A) in the general population?

DKC1 p.Pro97Thr (c.289C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DKC1 p.Pro97Thr (c.289C>A)?

AlphaMissense predicts likely pathogenic (score 0.9546) — an in-silico prediction, not a clinical call.

DKC1 p.Pro97Thr

c.289C>A · rs1557264153 · VCV452258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9546 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9546	likely pathogenic
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -12.16	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 7.7	GERP 4.2, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 4,035 bp · p 1.8e-12 · regional, not allelic
Overall
CADD	26.6	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.Pro97Thr
Coding: c.289C>A
MANE Select: NM_001363
dbSNP: rs1557264153
Type: single nucleotide variant
Location: chrX:154766241 (GRCh38)
Structure: AlphaFold pLDDT 79.74 · 7 PDB

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

Similar variants

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 p.Thr66Ala Pathogenic/Likely 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-pro97thr (accessed [today's date]).

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