PDX1 p.Pro33=
c.99T>C · rs925409013 · VCV755324
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00349%, nfe)
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 -9.8 | GERP -3.9 |
| Overall | ||
| CADD | 3.858 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00349%
European (non-Finnish) · 40/1,145,928 alleles
Filtering AF
0.00263%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00232%
Overall
0.00265%
41/1,548,152 alleles · very rare
exomes 41/1,395,956 · genomes 0/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00349% | 28,648 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,968 |
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
- PDX1
- Protein
- p.Pro33=
- Coding
- c.99T>C
- MANE Select
- NM_000209
- dbSNP
- rs925409013
- Type
- single nucleotide variant
- Location
- chr13:27920237 (GRCh38)
- Gene constraint
- LOEUF 1.642 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.99 · 2 PDB
- Residue 33
- the 'transactivation domain' region
Similar variants
- PDX1 p.Pro33His Uncertain significance ★★ ⚠ same residue
- PDX1 p.Pro33Ser Uncertain significance ★★ ⚠ same residue
- PDX1 p.Pro33Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
- PDX1 p.Pro33Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
- PDX1 p.Glu178Lys Pathogenic/Likely pathogenic ★★ same type
- PDX1 p.Lys191Gln Likely pathogenic ★★ same type
- PDX1 p.Ala10Thr Uncertain significance ★★ ⚠ same type
- PDX1 p.Ala152Val 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/pdx1-p-pro33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown