OTC p.Arg26=
c.78G>A · rs141273695 · VCV3045533
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00879%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.6 | GERP 0.19, phastCons 1 |
| Overall | ||
| CADD | 8.137 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00879%
African / African-American · 5/56,908 alleles
Filtering AF
0.0034%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00216%
Overall
0.000499%
6/1,202,878 alleles · very rare
exomes 1/1,091,335 · genomes 5/111,543 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00879% | 11,382 |
| Remaining individualsnot grpmax-eligible | 0.00211% | 47,352 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- OTC
- Protein
- p.Arg26=
- Coding
- c.78G>A
- MANE Select
- NM_000531
- dbSNP
- rs141273695
- Type
- single nucleotide variant
- Location
- chrX:38367291 (GRCh38)
- Structure
- AlphaFold pLDDT 91.94 · 4 PDB
- Residue 26
- a UniProt-annotated variant site (in otcd)
Similar variants
- OTC p.Arg26Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
- OTC p.Arg26Trp Uncertain significance ★★ ⚠ same residue
- OTC p.Arg26Leu Likely pathogenic ★ ⚠ same residue
- OTC p.Arg26Pro Pathogenic ⚠ same residue
- OTC c.298+2T>G Pathogenic ★★ same condition
- OTC c.299-1G>A Likely pathogenic ★★ same condition
- OTC c.386+1G>A Pathogenic ★★ same condition
- OTC c.540+1G>A Pathogenic ★★ 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/otc-p-arg26 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown