Is PCCA p.Pro166fs (c.497del) pathogenic?

PCCA p.Pro166fs (c.497del) is classified Pathogenic/Likely pathogenic in PCCA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-21). No gnomAD frequency available for this variant; Associated with propionic acidemia.

What condition is associated with PCCA p.Pro166fs (c.497del)?

PCCA p.Pro166fs (c.497del) is associated with propionic acidemia (ClinVar).

How common is PCCA p.Pro166fs (c.497del) in the general population?

PCCA p.Pro166fs (c.497del) 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.

PCCA p.Pro166fs

c.497del · rs2547726575 · VCV2748441

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -2.1, phastCons 0.99

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: PCCA
Protein: p.Pro166fs
Coding: c.497del
MANE Select: NM_000282
dbSNP: rs2547726575
Type: Deletion
Location: chr13:100209359 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 26 PDB
Residue 166: the biotin carboxylation domain

Full PCCA 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

PCCA p.Pro166Thr Likely pathogenic ★ same residue
PCCA p.Pro166Leu Uncertain significance ★ ⚠ same residue
PCCA p.Pro166= Likely benign ★ same residue
PCCA c.1899+4_1899+7del Pathogenic/Likely pathogenic ★★ same condition
PCCA p.Ala14fs Pathogenic/Likely pathogenic ★★ same condition
PCCA p.Arg390fs Pathogenic/Likely pathogenic ★★ same condition
PCCA p.Arg493fs Pathogenic ★★ same condition
PCCA p.Asn281fs 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-pro166fs (accessed [today's date]).

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