IMPDH1 p.Pro58Ser
c.172C>T · VCV4897747
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.02 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.34 | GERP -1.9 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 6,191 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 3.562 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,026 alleles
Overall
6.2e-05%
1/1,614,198 alleles · very rare
exomes 1/1,461,878 · genomes 0/152,320 · joint denominator
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
- IMPDH1
- Protein
- p.Pro58Ser
- Coding
- c.172C>T
- MANE Select
- NM_000883
- Type
- single nucleotide variant
- Location
- chr7:128409459 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
- Residue 58
- a β-strand
Similar variants
- IMPDH1 p.Arg309Pro Pathogenic/Likely pathogenic ★★ same type
- IMPDH1 p.Asp311Asn Pathogenic/Likely pathogenic ★★ same type
- IMPDH1 p.Asp311Gly Pathogenic/Likely pathogenic ★★ same type
- IMPDH1 p.Leu270Arg Likely pathogenic ★★ same type
- IMPDH1 p.Lys314Asn Pathogenic/Likely pathogenic ★★ same type
- IMPDH1 p.Lys323Arg Pathogenic/Likely pathogenic ★★ same type
- IMPDH1 c.1075-3C>T Uncertain significance ★★ same type
- IMPDH1 c.1551-5C>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/impdh1-p-pro58ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown