DKC1 p.Lys291Glu
c.871A>G · VCV3337026
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4425 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4425 | ambiguous |
|---|---|---|
| REVEL | 0.417 | indeterminate |
| SaProt | LLR -9.34 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 4.2, phastCons 1 |
| Regional constraint | o/e 0.29 | constrained · MANE · 8,165 bp · p 2.1e-24 · regional, not allelic |
| Overall | ||
| CADD | 22.3 | 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.Lys291Glu
- Coding
- c.871A>G
- MANE Select
- NM_001363
- Type
- single nucleotide variant
- Location
- chrX:154769266 (GRCh38)
- Structure
- AlphaFold pLDDT 79.74 · 7 PDB
- Residue 291
- an α-helix
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-lys291glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown