PDHX p.Val263=
c.789A>G · rs755428861 · VCV513956
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 -5.9 | GERP -4.2 |
| Overall | ||
| CADD | 0.181 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00204%
33/1,613,850 alleles · ultra-rare
exomes 30/1,461,832 · genomes 3/152,018 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| African / African-American | 0.00267% | 37,440 |
| European (non-Finnish) | 0.00237% | 42,142 |
| South Asian | 0.0011% | 91,064 |
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.Val263=
- Coding
- c.789A>G
- MANE Select
- NM_003477
- dbSNP
- rs755428861
- Type
- single nucleotide variant
- Location
- chr11:34966787 (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 263
- the 'disordered' region
Similar variants
- 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
- PDHX p.Ala236Asp 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-val263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown