Propionic acidemia: genes and variants
Explore variant evidence for Propionic acidemia across 2 analyzed proteins (PCCB, PCCA). Linked ClinVar records include 107 pathogenic or likely pathogenic variants, 560 variants of uncertain significance and 68 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Counts refer to the selected disease label.
Data updated 2026-10-11. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Propionic acidemia
PCCB: Propionyl-CoA carboxylase beta chain, mitochondrial
The beta subunit of mitochondrial propionyl-CoA carboxylase, a biotin-dependent enzyme in amino-acid and fatty-acid breakdown. Variants cause propionic acidemia.
71 ClinVar pathogenic / likely pathogenic and 291 uncertain variants in PCCB have source records linked to Propionic acidemia. Association strength is not clinical gene validity.
PCCA: Propionyl-CoA carboxylase alpha chain, mitochondrial
The alpha subunit of mitochondrial propionyl-CoA carboxylase, which processes propionyl-CoA from certain amino acids and fatty acids. Variants cause propionic acidemia.
36 ClinVar pathogenic / likely pathogenic and 337 uncertain variants in PCCA have source records linked to Propionic acidemia. Association strength is not clinical gene validity.
ClinVar pathogenic and likely pathogenic variants linked to Propionic acidemia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| PCCA R77Q | 77 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA R288K | 288 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| PCCA R288G | 288 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| PCCA R399Q | 399 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCB G162W | 162 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB G162R | 162 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R165Q | 165 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB P279L | 279 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R376C | 376 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB F391S | 391 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB G437S | 437 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCA R230H | 230 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| PCCA R230C | 230 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| PCCB R165P | 165 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R165W | 165 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB G245S | 245 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R410Q | 410 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R410W | 410 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R512H | 512 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCA A106E | 106 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA Y121C | 121 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA A138T | 138 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA I164T | 164 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA M373K | 373 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| PCCA G456V | 456 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA G668R | 668 | Biotinyl-binding | Pathogenic / likely pathogenic (★★) |
| PCCB V107M | 107 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB A153P | 153 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB E168K | 168 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB G198D | 198 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB S363P | 363 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB P399R | 399 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB A454V | 454 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB L519P | 519 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCA R77W | 77 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA E261G | 261 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| PCCA K298R | 298 | ATP-grasp | Pathogenic / likely pathogenic (★★) |
| PCCB M1I | 1 | Pathogenic / likely pathogenic (★★) | |
| PCCB Q58P | 58 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB G188R | 188 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB V205D | 205 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB M316R | 316 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R376L | 376 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB D382E | 382 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB A434V | 434 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB Y435C | 435 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB A438V | 438 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB Y439C | 439 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB R512C | 512 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCA P423L | 423 | Biotin carboxylation | Pathogenic / likely pathogenic (★★) |
| PCCA G631R | 631 | Pathogenic / likely pathogenic (★★) | |
| PCCB G255S | 255 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB E404K | 404 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB I430L | 430 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB G112D | 112 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB T428I | 428 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB A458V | 458 | CoA carboxyltransferase C-terminal | Pathogenic / likely pathogenic (★★) |
| PCCB N536D | 536 | Pathogenic / likely pathogenic (★★) | |
| PCCA R399W | 399 | Biotin carboxylation | Pathogenic / likely pathogenic (★) |
| PCCB G245C | 245 | CoA carboxyltransferase N-terminal | Pathogenic / likely pathogenic (★) |
Showing 60 of 107.
Uncertain variants prioritized for review in Propionic acidemia
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| PCCB G437D | 437 | CoA carboxyltransferase C-terminal | Conflicting reports (★) | +7: 6 other pathogenic changes within 3 positions; G437C at the same position is pathogenic; seen in 1.4e-06 of gnomAD DNA copies; REVEL 0.983 |
| PCCB G245D | 245 | CoA carboxyltransferase N-terminal | Conflicting reports (★) | +7: 4 other pathogenic changes within 3 positions; G245S at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.964 |
| PCCB G112S | 112 | CoA carboxyltransferase N-terminal | Conflicting reports (★) | +7: G112D at the same position is pathogenic; seen in 1.4e-06 of gnomAD DNA copies; REVEL 0.937 |
| PCCB R376G | 376 | CoA carboxyltransferase C-terminal | Conflicting reports (★) | +7: 2 other pathogenic changes within 3 positions; R376L at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.974 |
| PCCA M373V | 373 | ATP-grasp | Conflicting reports (★) | +7: M373K at the same position is pathogenic; seen in 6.8e-07 of gnomAD DNA copies; REVEL 0.959 |
| PCCA P166L | 166 | Biotin carboxylation | Uncertain (★) | +7: 2 other pathogenic changes within 3 positions; P166T at the same position is pathogenic; seen in 2e-06 of gnomAD DNA copies; REVEL 0.987 |
| PCCB Q58R | 58 | CoA carboxyltransferase N-terminal | Uncertain | +7: 2 other pathogenic changes within 3 positions; Q58P at the same position is pathogenic; not seen in the gnomAD population database; REVEL 0.890 |
| PCCB P154S | 154 | CoA carboxyltransferase N-terminal | Uncertain (★★) | +7: 2 other pathogenic changes within 3 positions; P154L at the same position is pathogenic; seen in 7.1e-07 of gnomAD DNA copies; REVEL 0.954 |
| PCCB G412D | 412 | CoA carboxyltransferase C-terminal | Uncertain (★★) | +7: 3 other pathogenic changes within 3 positions; G412S at the same position is pathogenic; seen in 6.8e-07 of gnomAD DNA copies; REVEL 0.950 |
| PCCB P399S | 399 | CoA carboxyltransferase C-terminal | Uncertain (★) | +7: P399R at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.932 |
| PCCA Y121S | 121 | Biotin carboxylation | Uncertain (★) | +7: in a 3D region that tolerates change poorly (1R); Y121C at the same position is pathogenic; seen in 6.8e-07 of gnomAD DNA copies; REVEL 0.971 |
| PCCB A438D | 438 | CoA carboxyltransferase C-terminal | Conflicting reports (★) | +6: 5 other pathogenic changes within 3 positions; A438V at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 1.00 |
| PCCB R376H | 376 | CoA carboxyltransferase C-terminal | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R376L at the same position is pathogenic; REVEL 0.965 |
| PCCA R268C | 268 | ATP-grasp | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R268L at the same position is pathogenic; REVEL 0.910 |
| PCCB S363L | 363 | CoA carboxyltransferase C-terminal | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; S363P at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.58 |
| PCCB I505T | 505 | CoA carboxyltransferase C-terminal | Conflicting reports (★) | +6: I505N at the same position is pathogenic; REVEL 0.963 |
| PCCB H59Q | 59 | CoA carboxyltransferase N-terminal | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; H59N at the same position is pathogenic; seen in 0 of gnomAD DNA copies; REVEL 0.723 |
| PCCB A458T | 458 | CoA carboxyltransferase C-terminal | Uncertain (★★) | +6: A458V at the same position is pathogenic; REVEL 0.960 |
| PCCA A320T | 320 | ATP-grasp | Uncertain (★) | +6: in a 3D region that tolerates change poorly (3R); A320D at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.75 |
| PCCA R268H | 268 | ATP-grasp | Uncertain (★★) | +6: 2 other pathogenic changes within 3 positions; R268L at the same position is pathogenic; REVEL 0.945 |
| PCCB H59Y | 59 | CoA carboxyltransferase N-terminal | Uncertain (★★) | +6: 2 other pathogenic changes within 3 positions; H59N at the same position is pathogenic; REVEL 0.913 |
| PCCB D382G | 382 | CoA carboxyltransferase C-terminal | Uncertain (★★) | +6: 2 other pathogenic changes within 3 positions; D382E at the same position is pathogenic; REVEL 0.989 |
| PCCB T235A | 235 | CoA carboxyltransferase N-terminal | Uncertain (★★) | +6: T235P at the same position is pathogenic; REVEL 0.968 |
| PCCB A438S | 438 | CoA carboxyltransferase C-terminal | Uncertain (★) | +6: 5 other pathogenic changes within 3 positions; A438V at the same position is pathogenic; REVEL 0.851 |
| PCCB V205I | 205 | CoA carboxyltransferase N-terminal | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; V205D at the same position is pathogenic; REVEL 0.788 |
| PCCB M316V | 316 | CoA carboxyltransferase C-terminal | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; M316R at the same position is pathogenic; REVEL 0.895 |
| PCCB A267S | 267 | CoA carboxyltransferase N-terminal | Uncertain (★) | +6: in a 3D region that tolerates change poorly (1R); A267D at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.771 |
Which prediction tools work for Propionic acidemia
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaGenome (regulatory): 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 93 out of 100
- REVEL: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 90 out of 100
- SIFT: 88 out of 100
- ESM1b (LLR): 88 out of 100
- phyloP: 84 out of 100
- AlphaGenome (splicing): 36 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Frequently asked questions
Which genes have records linked to Propionic acidemia?
This view contains 2 analyzed proteins: PCCB, PCCA. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 107 pathogenic or likely pathogenic variants, 560 variants of uncertain significance and 68 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 27 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 820 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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