IMPDH1 p.Pro4=
c.12A>G · rs978197671 · VCV1591760
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00797%, amr)
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 -0.4 | GERP -2.1, phastCons 0.16 |
| Overall | ||
| CADD | 7.635 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00797%
Admixed American · 3/37,662 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00113%
Overall
0.000556%
8/1,438,418 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00797% | 12,554 |
| African / African-American | 0.00594% | 16,823 |
| Remaining individualsnot grpmax-eligible | 0.00181% | 55,114 |
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.Pro4=
- Coding
- c.12A>G
- MANE Select
- NM_000883
- dbSNP
- rs978197671
- Type
- single nucleotide variant
- Location
- chr7:128409890 (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.Pro4Ser Uncertain significance ★★ 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-pro4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown