IMPDH1 p.Phe126Ser
c.377T>C · rs367549284 · VCV444730
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0967%, amr)
Conditions
3
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.616 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP -0.67, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 6,191 bp · p 0.96 · regional, not allelic |
| Overall | ||
| CADD | 24.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0967%
Admixed American · 58/60,008 alleles
Filtering AF
0.0767%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0696%
Overall
0.00397%
64/1,614,026 alleles · ultra-rare
exomes 46/1,461,790 · genomes 18/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0967% | 1,035 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| African / African-American | 0.004% | 24,977 |
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.Phe126Ser
- Coding
- c.377T>C
- MANE Select
- NM_000883
- dbSNP
- rs367549284
- Type
- single nucleotide variant
- Location
- chr7:128403731 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.71 · 18 PDB
- Residue 126
- the cbs 1 domain
Similar variants
- IMPDH1 p.Arg309Pro Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Asp311Asn Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Lys314Asn Pathogenic/Likely pathogenic ★★ same condition
- IMPDH1 p.Lys323Arg Pathogenic/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.Ala477Thr 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-phe126ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown