GMPPB p.Ile75=
c.225C>T · rs945019622 · VCV514184
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 2.2 | GERP -0.56, phastCons 1 |
| Overall | ||
| CADD | 9.127 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,074 alleles
Overall
0.000137%
2/1,461,854 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 75,074 |
| European (non-Finnish) | 8.47e-05% | 1,180,032 |
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
- GMPPB
- Protein
- p.Ile75=
- Coding
- c.225C>T
- MANE Select
- NM_021971
- dbSNP
- rs945019622
- Type
- single nucleotide variant
- Location
- chr3:49723288 (GRCh38)
- Gene constraint
- LOEUF 1.189 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.33 · 3 PDB
- Residue 75
- the 'substrate-binding domain' region; a β-strand
Similar variants
- GMPPB c.129+1G>T Likely pathogenic ★★ same type
- GMPPB c.402+1G>A Pathogenic/Likely pathogenic ★★ same type
- GMPPB c.640+1G>A Pathogenic/Likely pathogenic ★★ same type
- GMPPB c.640+1G>C Likely pathogenic ★★ same type
- GMPPB p.Arg185Cys Pathogenic/Likely pathogenic ★★ same type
- GMPPB p.Arg287Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- GMPPB p.Arg287Trp Pathogenic ★★ same type
- GMPPB p.Asp27His Pathogenic/Likely 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/gmppb-p-ile75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown