Is PCCB p.Val205Ile (c.613G>A) pathogenic?

PCCB p.Val205Ile (c.613G>A) is classified Uncertain significance in PCCB (ClinVar, Single submitter, 2 submitters; last evaluated 2022-08-01). AlphaMissense: likely pathogenic (0.5895); Very rare (popmax 0.00874%, nfe); Associated with propionic acidemia.

What condition is associated with PCCB p.Val205Ile (c.613G>A)?

PCCB p.Val205Ile (c.613G>A) is associated with propionic acidemia (ClinVar).

How common is PCCB p.Val205Ile (c.613G>A) in the general population?

PCCB p.Val205Ile (c.613G>A) is very rare (popmax 0.00874%, nfe) (gnomAD).

How is Propionic acidemia inherited?

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

What do computational predictors say about PCCB p.Val205Ile (c.613G>A)?

AlphaMissense predicts likely pathogenic (score 0.5895) — an in-silico prediction, not a clinical call.

PCCB p.Val205Ile

c.613G>A · rs141956198 · VCV972656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5895 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00874%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

propionic acidemia

Computational evidence

Protein change
AlphaMissense	0.5895	likely pathogenic
REVEL	0.788	moderately pathogenic-leaning
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 80 kb · p 0.017 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00874% European (non-Finnish) · 103/1,178,940 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00685%

Overall 0.00663% 107/1,612,870 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00874%	11,446
Remaining individualsnot grpmax-eligible	0.0016%	62,466
Finnishnot grpmax-eligible	0.00156%	64,014
African / African-American	0.00133%	75,008
South Asian	0.0011%	91,056

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.Val205Ile
Coding: c.613G>A
MANE Select: NM_000532
dbSNP: rs141956198
Type: single nucleotide variant
Location: chr3:136283906 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 205: the coa carboxyltransferase n-terminal domain; a UniProt-annotated variant site (in pa-2); 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.Val205Asp Pathogenic ★★ same residue
PCCB p.Val205Gly Likely pathogenic ★ ⚠ same residue
PCCB c.1199-1G>A Pathogenic/Likely pathogenic ★★ same condition
PCCB c.1199-2A>G Pathogenic ★★ same condition
PCCB c.1398+1G>C Pathogenic/Likely pathogenic ★★ same condition
PCCB c.1398+1G>T Pathogenic/Likely pathogenic ★★ same condition
PCCB c.1498+2T>C Pathogenic ★★ same condition
PCCB c.1499-1G>C 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/pccb-p-val205ile (accessed [today's date]).

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