IMPDH1 p.Phe541=
c.1623C>T · rs749416988 · VCV285033
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0351%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.9 | GERP -3.7 |
| Overall | ||
| CADD | 15.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0351%
South Asian · 32/91,084 alleles
Filtering AF
0.0256%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0222%
Overall
0.00514%
83/1,613,844 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0351% | 2,846 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,926 |
| European (non-Finnish) | 0.00339% | 29,499 |
| Admixed American | 0.00333% | 30,000 |
| African / African-American | 0.00267% | 37,447 |
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.Phe541=
- Coding
- c.1623C>T
- MANE Select
- NM_000883
- dbSNP
- rs749416988
- Type
- single nucleotide variant
- Location
- chr7:128394527 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
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-phe541 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown