IMPDH1 p.Ser581=
c.1743G>A · rs765536215 · VCV1626338
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00695%, nfe)
Conditions
1
inherited retinal dystrophy
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 -9.9 | GERP -3.7 |
| Overall | ||
| CADD | 6.935 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00695%
European (non-Finnish) · 82/1,179,986 alleles
Filtering AF
0.00571%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00525%
Overall
0.00558%
90/1,613,918 alleles · very rare
exomes 86/1,461,828 · genomes 4/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00695% | 14,390 |
| Admixed American | 0.005% | 20,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| East Asian | 0.00223% | 44,864 |
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.Ser581=
- Coding
- c.1743G>A
- MANE Select
- NM_000883
- dbSNP
- rs765536215
- Type
- single nucleotide variant
- Location
- chr7:128394313 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
Similar variants
- IMPDH1 p.Ser581Leu 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-ser581 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown