MOCS2 p.Arg22Pro
c.65G>C · rs577168655 · VCV1491470
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
sulfite oxidase deficiency due to molybdenum cofactor deficiency type B1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.49 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -0.86, phastCons 0.95 |
| Overall | ||
| CADD | 17.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,828 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000248%
4/1,613,410 alleles · very rare
exomes 4/1,461,120 · genomes 0/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,828 |
| South Asian | 0.0022% | 45,514 |
| European (non-Finnish) | 8.48e-05% | 1,179,508 |
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
- MOCS2
- Protein
- p.Arg22Pro
- Coding
- c.65G>C
- MANE Select
- NM_004531 · reported on NM_176806
- dbSNP
- rs577168655
- Type
- single nucleotide variant
- Location
- chr5:53108597 (GRCh38)
- Gene constraint
- LOEUF 1.066 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.07 · 2 PDB
- Residue 22
- a β-strand; a UniProt-annotated variant site (in mocodb1)
Similar variants
- MOCS2 p.Pro22Ala Uncertain significance ★★ ⚠ same residue
- MOCS2 p.Pro22Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- MOCS2 p.Pro22Leu Likely benign ★★ same residue
- MOCS2 p.Arg22Leu Uncertain significance ★ same residue
- MOCS2 p.Pro22= Likely benign ★ same residue
- MOCS2 p.Pro22Gln Likely benign ★ same residue
- MOCS2 c.377+1G>A Pathogenic/Likely pathogenic ★★ same condition
- MOCS2 p.Gln30Ter Pathogenic/Likely 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/mocs2-p-arg22pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown