OTC p.Lys221=
c.663G>A · rs281865552 · VCV97286
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.83 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.48 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 21.1 | PHRED · no single calibrated threshold — expert panels disagree |
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
- OTC
- Protein
- p.Lys221=
- Coding
- c.663G>A
- MANE Select
- NM_000531
- dbSNP
- rs281865552
- Type
- single nucleotide variant
- Location
- chrX:38403740 (GRCh38)
- Structure
- AlphaFold pLDDT 91.94 · 4 PDB
- Residue 221
- a modified residue (n6-acetyllysine; alternate); a modified residue (n6-succinyllysine; alternate)
Similar variants
- OTC p.Lys221Asn Pathogenic/Likely pathogenic ★★ ⚠ same residue
- OTC p.Lys221Arg Uncertain significance ★ ⚠ same residue
- OTC c.298+2T>G Pathogenic ★★ same type
- OTC c.299-1G>A Likely pathogenic ★★ same type
- OTC c.386+1G>A Pathogenic ★★ same type
- OTC c.540+1G>A Pathogenic ★★ same type
- OTC c.540+1G>T Pathogenic ★★ same type
- OTC c.540+265G>A Pathogenic ★★ 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/otc-p-lys221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown