Is PCCA p.Val6= (c.18C>T) pathogenic?

PCCA p.Val6= (c.18C>T) is classified Likely benign in PCCA (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-06). Very rare (popmax 8.87e-05%, nfe); Associated with propionic acidemia.

What condition is associated with PCCA p.Val6= (c.18C>T)?

PCCA p.Val6= (c.18C>T) is associated with propionic acidemia (ClinVar).

How common is PCCA p.Val6= (c.18C>T) in the general population?

PCCA p.Val6= (c.18C>T) is very rare (popmax 8.87e-05%, nfe) (gnomAD).

How is Propionic acidemia inherited?

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

PCCA p.Val6=

c.18C>T · rs752423629 · VCV1102071

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.87e-05%, nfe)

Conditions

propionic acidemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4
Overall
CADD	0.981	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.87e-05% European (non-Finnish) · 1/1,127,518 alleles

Overall 6.63e-05% 1/1,508,840 alleles · very rare exomes 1/1,356,526 · genomes 0/152,314 · 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.Val6=
Coding: c.18C>T
MANE Select: NM_000282
dbSNP: rs752423629
Type: single nucleotide variant
Location: chr13:100089138 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 26 PDB

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.Val6fs Pathogenic/Likely pathogenic ★★ same residue
PCCA p.Val6Ala 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

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-val6 (accessed [today's date]).

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