Is PCCB p.Phe330Val (c.988T>G) pathogenic?

PCCB p.Phe330Val (c.988T>G) is classified Uncertain significance in PCCB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-11). AlphaMissense: ambiguous (0.4512); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with PCCB p.Phe330Val (c.988T>G)?

PCCB p.Phe330Val (c.988T>G) is associated with Inborn genetic diseases, propionic acidemia (ClinVar).

How common is PCCB p.Phe330Val (c.988T>G) in the general population?

PCCB p.Phe330Val (c.988T>G) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about PCCB p.Phe330Val (c.988T>G)?

AlphaMissense predicts ambiguous (score 0.4512) — an in-silico prediction, not a clinical call.

PCCB p.Phe330Val

c.988T>G · rs748708704 · VCV653691

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4512 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4512	ambiguous
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -11.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 80 kb · p 0.017 · regional, not allelic
Overall
CADD	27.3	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 0.015% Admixed American · 9/60,004 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00316% 51/1,614,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,667
Remaining individualsnot grpmax-eligible	0.0048%	20,826
South Asian	0.00439%	22,772
European (non-Finnish)	0.00297%	33,715

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.Phe330Val
Coding: c.988T>G
MANE Select: NM_000532
dbSNP: rs748708704
Type: single nucleotide variant
Location: chr3:136316962 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 330: the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region; the 'acyl-coa binding' region; a β-strand

Full PCCB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: propionic acidemia

Similar variants

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
PCCB c.183+1G>A Pathogenic/Likely pathogenic ★★ same condition
PCCB c.183+5G>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/pccb-p-phe330val (accessed [today's date]).

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