IMPDH1 p.Ala321Val
c.962C>T · rs1584728088 · VCV636038
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
3
IMPDH1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.946 | strongly pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.72 | unconstrained · MANE · 11 kb · p 1.3e-12 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- IMPDH1
- Protein
- p.Ala321Val
- Coding
- c.962C>T
- MANE Select
- NM_000883
- dbSNP
- rs1584728088
- Type
- single nucleotide variant
- Location
- chr7:128398526 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
- Residue 321
- a β-strand
Disease context
IMPDH1-related disorder
Also linked: inherited retinal dystrophyretinitis pigmentosa
Similar variants
- IMPDH1 p.Arg309Pro Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Asp311Asn Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Asp311Gly Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Leu270Arg Likely pathogenic ★★ same condition
- IMPDH1 c.1075-3C>T Uncertain significance ★★ same condition
- IMPDH1 c.*137G>C Uncertain significance ★★ same condition
- IMPDH1 c.*721G>A Uncertain significance ★★ same condition
- IMPDH1 p.Arg142Trp Uncertain significance ★★ 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-ala321val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown