IMPDH1 p.Pro99=
c.297C>G · rs1415042353 · VCV3027899
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00394%, amr)
Conditions
1
inherited retinal dystrophy
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 -0.45 | GERP -3.3, phastCons 0.014 |
| Overall | ||
| CADD | 10.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00394%
Admixed American · 2/50,788 alleles
Filtering AF
0.000653%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000244%
Overall
0.000216%
3/1,389,220 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00394% | 25,394 |
| European (non-Finnish) | 8.73e-05% | 1,145,466 |
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.Pro99=
- Coding
- c.297C>G
- MANE Select
- NM_000883
- dbSNP
- rs1415042353
- Type
- single nucleotide variant
- Location
- chr7:128405823 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
- Residue 99
- an α-helix
Similar variants
- IMPDH1 p.Pro99Arg Uncertain significance ★ same residue
- IMPDH1 p.Arg309Pro Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Asp311Asn Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Leu270Arg Likely pathogenic ★★ same condition
- IMPDH1 p.Arg407Cys Uncertain significance ★★ same condition
- IMPDH1 p.Arg492Trp Uncertain significance ★★ same condition
- IMPDH1 p.Ala525= Benign ★★ same condition
- IMPDH1 p.Gln512= Benign/Likely benign ★★ same condition
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-pro99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown