IMPDH1 p.Pro4Ser
c.10C>T · rs1380986603 · VCV1913557
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00594%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.053 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 1.3, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 6,191 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 20.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00594%
East Asian · 2/33,674 alleles
Filtering AF
0.000984%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000368%
Overall
0.000468%
6/1,281,550 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00594% | 16,837 |
| European (non-Finnish) | 0.000364% | 274,416 |
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.Pro4Ser
- Coding
- c.10C>T
- MANE Select
- NM_000883
- dbSNP
- rs1380986603
- Type
- single nucleotide variant
- Location
- chr7:128409892 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
- Residue 4
- an α-helix
Similar variants
- IMPDH1 p.Pro4= Likely benign ★ same residue
- 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
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-pro4ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown