Is PCCB p.Phe129Ter (c.386delinsAA) pathogenic?

PCCB p.Phe129Ter (c.386delinsAA) is classified Pathogenic in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). No gnomAD frequency available for this variant; Associated with propionic acidemia.

What condition is associated with PCCB p.Phe129Ter (c.386delinsAA)?

PCCB p.Phe129Ter (c.386delinsAA) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Phe129Ter (c.386delinsAA) in the general population?

PCCB p.Phe129Ter (c.386delinsAA) is no gnomAD frequency available for this variant (gnomAD).

How is Propionic acidemia inherited?

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

PCCB p.Phe129Ter

c.386delinsAA · rs2529760174 · VCV2782920

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

propionic acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PCCB
Protein: p.Phe129Ter
Coding: c.386delinsAA
MANE Select: NM_000532
dbSNP: rs2529760174
Type: Indel
Location: chr3:136260492 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 129: the coa carboxyltransferase n-terminal domain; the 'carboxyltransferase' region; an α-helix

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.Phe129= Likely benign ★ same residue
PCCB p.Phe129fs Likely pathogenic ★ same residue
PCCB p.Asp273fs Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Asp56_Lys60delinsAla Pathogenic ★★ same condition
PCCB c.184-49_188delinsTGCTTTGCTTGCTTTGCTTTGCTTT Pathogenic ★ same condition
PCCB c.77_183+30delinsCC Likely pathogenic ★ same condition
PCCB p.? Pathogenic ★ same condition
PCCB p.Ala204fs 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/pccb-p-phe129ter (accessed [today's date]).

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