PDHA1 p.His154=
c.462C>T · VCV3384758
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000112%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.5 | GERP -3.9, phastCons 0.056 |
| Overall | ||
| CADD | 2.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000112%
European (non-Finnish) · 1/894,192 alleles
Overall
9.12e-05%
1/1,096,690 alleles · very rare
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
- PDHA1
- Protein
- p.His154=
- Coding
- c.462C>T
- MANE Select
- NM_000284
- Type
- single nucleotide variant
- Location
- chrX:19353125 (GRCh38)
- Structure
- AlphaFold pLDDT 94.77 · 9 PDB
Similar variants
- PDHA1 p.His154Arg Likely pathogenic ★ same residue
- PDHA1 p.Ala169Val Pathogenic ★★★ same type
- PDHA1 p.Arg304Ter Pathogenic ★★★ same type
- PDHA1 p.Arg378Cys Pathogenic ★★★ ⚠ same type
- PDHA1 p.Arg72Cys Likely pathogenic ★★★ same type
- PDHA1 p.Ile280Ser Uncertain significance ★★★ ⚠ same type
- PDHA1 p.Ala265= Benign ★★★ same type
- PDHA1 p.Glu333Asp Benign ★★★ 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/pdha1-p-his154 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown