Is PCCA p.Phe494= (c.1482T>C) pathogenic?

PCCA p.Phe494= (c.1482T>C) is classified Likely benign in PCCA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-27). Very rare (popmax 0.00133%, afr); Associated with propionic acidemia.

What condition is associated with PCCA p.Phe494= (c.1482T>C)?

PCCA p.Phe494= (c.1482T>C) is associated with propionic acidemia (ClinVar).

How common is PCCA p.Phe494= (c.1482T>C) in the general population?

PCCA p.Phe494= (c.1482T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Propionic acidemia inherited?

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

PCCA p.Phe494=

c.1482T>C · rs2548249367 · VCV2134347

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

propionic acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.297	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP -1.5, phastCons 1
Overall
CADD	8.948	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,060 alleles

Overall 6.2e-05% 1/1,613,196 alleles · very rare exomes 1/1,460,850 · genomes 0/152,346 · 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: PCCA
Protein: p.Phe494=
Coding: c.1482T>C
MANE Select: NM_000282
dbSNP: rs2548249367
Type: single nucleotide variant
Location: chr13:100330613 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 26 PDB
Residue 494: an α-helix; 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 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
PCCA c.1746+1G>A 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-phe494 (accessed [today's date]).

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