Is PCCB p.Val342del (c.1022TTG[1]) pathogenic?

PCCB p.Val342del (c.1022TTG[1]) is classified Uncertain significance in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-28). Very rare (popmax 0.00134%, afr); Associated with propionic acidemia.

What condition is associated with PCCB p.Val342del (c.1022TTG[1])?

PCCB p.Val342del (c.1022TTG[1]) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Val342del (c.1022TTG[1]) in the general population?

PCCB p.Val342del (c.1022TTG[1]) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Propionic acidemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PCCB p.Val342del

c.1022TTG[1] · rs771030934 · VCV2781777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

propionic acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1	GERP -4.4
Overall
CADD	15.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,888 alleles

Overall 6.2e-05% 1/1,613,870 alleles · very rare exomes 0/1,461,782 · genomes 1/152,088 · joint denominator

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: PCCB
Protein: p.Val342del
Coding: c.1022TTG[1]
MANE Select: NM_000532
dbSNP: rs771030934
Type: Microsatellite
Location: chr3:136316996 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 342: the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region; the 'acyl-coa binding' region; a β-strand

Full PCCB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

propionic acidemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Propionic acidemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: >1 / 1000 (Canada)

Similar variants

PCCB p.Ile409del Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Ser123fs Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Thr428fs Pathogenic/Likely pathogenic ★★ same condition
PCCB c.303+19_303+21del Likely benign ★★ same condition
PCCB c.429+3_429+6del Likely pathogenic ★ same condition
PCCB p.Asp382fs Pathogenic ★ same condition
PCCB p.Glu168del Likely pathogenic ★ same condition
PCCB p.Ile196fs 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/pccb-p-val342del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown