Is PCCB p.Gly343Arg (c.1027G>C) pathogenic?

PCCB p.Gly343Arg (c.1027G>C) is classified Uncertain significance in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2015-01-06). AlphaMissense: likely pathogenic (0.9867); Very rare (popmax 8.48e-05%, nfe).

How common is PCCB p.Gly343Arg (c.1027G>C) in the general population?

PCCB p.Gly343Arg (c.1027G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PCCB p.Gly343Arg (c.1027G>C)?

AlphaMissense predicts likely pathogenic (score 0.9867) — an in-silico prediction, not a clinical call.

PCCB p.Gly343Arg

c.1027G>C · rs765394399 · VCV193599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9867 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9867	likely pathogenic · top 10% in PCCB
REVEL	0.977	strongly pathogenic-leaning
SaProt	LLR -14.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 80 kb · p 0.017 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,930 alleles

Overall 6.2e-05% 1/1,613,966 alleles · very rare exomes 1/1,461,804 · genomes 0/152,162 · 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: PCCB
Protein: p.Gly343Arg
Coding: c.1027G>C
MANE Select: NM_000532
dbSNP: rs765394399
Type: single nucleotide variant
Location: chr3:136317001 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 343: 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

Similar variants

PCCB c.1199-1G>A Pathogenic/Likely pathogenic ★★ same type
PCCB c.1199-2A>G Pathogenic ★★ same type
PCCB c.1398+1G>C Pathogenic/Likely pathogenic ★★ same type
PCCB c.1398+1G>T Pathogenic/Likely pathogenic ★★ same type
PCCB c.1498+2T>C Pathogenic ★★ same type
PCCB c.1499-1G>C Pathogenic/Likely pathogenic ★★ same type
PCCB c.183+1G>A Pathogenic/Likely pathogenic ★★ same type
PCCB c.183+5G>A Pathogenic/Likely pathogenic ★★ same type

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-gly343arg (accessed [today's date]).

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