IMPDH1 p.Pro21=
c.63C>T · rs958607869 · VCV1572597
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00434%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.53 | GERP -2.7, phastCons 0.005 |
| Overall | ||
| CADD | 13.81 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00434%
Admixed American · 2/46,102 alleles
Filtering AF
0.000719%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000269%
Overall
0.000201%
3/1,495,836 alleles · very rare
exomes 1/1,343,672 · genomes 2/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00434% | 23,051 |
| East Asian | 0.00276% | 36,168 |
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.Pro21=
- Coding
- c.63C>T
- MANE Select
- NM_000883
- dbSNP
- rs958607869
- Type
- single nucleotide variant
- Location
- chr7:128409839 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
- Residue 21
- an α-helix
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-pro21 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown