PDHX p.Pro233=
c.699A>G · VCV4812202
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
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 -1.7 | GERP -4.2 |
| Overall | ||
| CADD | 0.533 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00715%
Overall
0.00304%
49/1,614,002 alleles · ultra-rare
exomes 43/1,461,884 · genomes 6/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,028 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
| European (non-Finnish) | 0.00322% | 31,053 |
| Admixed American | 0.00167% | 59,988 |
| African / African-American | 0.00133% | 74,908 |
| South Asian | 0.0011% | 91,076 |
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
- PDHX
- Protein
- p.Pro233=
- Coding
- c.699A>G
- MANE Select
- NM_003477
- Type
- single nucleotide variant
- Location
- chr11:34966697 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.13 · 5 PDB
- Residue 233
- the 'disordered' region
Similar variants
- PDX1 p.Glu233Lys Uncertain significance ★ ⚠ same residue
- PDHX p.Arg284Ter Pathogenic ★★ same type
- PDHX p.Arg446Ter Pathogenic/Likely pathogenic ★★ same type
- PDHX p.Arg476Ter Likely pathogenic ★★ same type
- PDHX p.Gln248Ter Pathogenic ★★ same type
- PDHX p.Gln411Ter Pathogenic/Likely pathogenic ★★ same type
- PDX1 p.Lys191Gln Likely pathogenic ★★ same type
- PDHX c.1023+2267A>G 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/pdhx-p-pro233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown