PCCA p.Asp368=
c.1104C>T · VCV3717996
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
propionic acidemia
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 0.86 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 8.715 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PCCA
- Protein
- p.Asp368=
- Coding
- c.1104C>T
- MANE Select
- NM_000282
- Type
- single nucleotide variant
- Location
- chr13:100301498 (GRCh38)
- Gene constraint
- LOEUF 0.986 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 26 PDB
- Residue 368
- the biotin carboxylation domain; the atp-grasp domain; a UniProt-annotated variant site (in pa-1)
Disease context
propionic acidemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Propionic acidemia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- >1 / 1000 (Canada)
Similar variants
- PCCA p.Asp368His Uncertain significance ⚠ same residue
- PCCA c.105+1G>A Pathogenic ★★ same condition
- PCCA c.106-1G>A Likely pathogenic ★★ same condition
- PCCA c.1065+1G>A Likely pathogenic ★★ same condition
- PCCA c.1209+2T>G Likely pathogenic ★★ same condition
- PCCA c.1209+3A>G Pathogenic/Likely pathogenic ★★ same condition
- PCCA c.1284+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PCCA c.1540+1G>C Pathogenic/Likely pathogenic ★★ same condition
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/pcca-p-asp368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown