PDHX p.Pro344=
c.1032A>G · rs771477240 · VCV2060358
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0143%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.073 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.19 | GERP -3.1 |
| Overall | ||
| CADD | 4.659 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0143%
European (non-Finnish) · 169/1,179,932 alleles
Filtering AF
0.0125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0119%
Overall
0.0108%
174/1,613,892 alleles · ultra-rare
exomes 163/1,461,714 · genomes 11/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0143% | 6,982 |
| African / African-American | 0.004% | 24,971 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
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.Pro344=
- Coding
- c.1032A>G
- MANE Select
- NM_003477
- dbSNP
- rs771477240
- Type
- single nucleotide variant
- Location
- chr11:34984578 (GRCh38)
- Gene constraint
- LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.13 · 5 PDB
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-pro344 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown