Is PCCB p.Gln58Pro (c.173A>C) pathogenic?

PCCB p.Gln58Pro (c.173A>C) is classified Likely pathogenic in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely pathogenic (0.9405); Very rare (popmax 0.00305%, nfe).

How common is PCCB p.Gln58Pro (c.173A>C) in the general population?

PCCB p.Gln58Pro (c.173A>C) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about PCCB p.Gln58Pro (c.173A>C)?

AlphaMissense predicts likely pathogenic (score 0.9405) — an in-silico prediction, not a clinical call.

PCCB p.Gln58Pro

c.173A>C · rs763949276 · VCV3026524

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9405	likely pathogenic ✓ concordant with ClinVar
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -14.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
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	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 0.00305% European (non-Finnish) · 36/1,179,570 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00223% 36/1,612,160 alleles · very rare exomes 36/1,459,792 · genomes 0/152,368 · 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.Gln58Pro
Coding: c.173A>C
MANE Select: NM_000532
dbSNP: rs763949276
Type: single nucleotide variant
Location: chr3:136250548 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 58: the coa carboxyltransferase n-terminal domain; the 'carboxyltransferase' region; an α-helix

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

Similar variants

PCCB p.Gln58Ter Pathogenic ★ same residue
PCCB p.Gln58= Likely benign ★ same residue
PCCB p.Gln58Arg Uncertain significance ⚠ same residue
PCCB p.Gln58_His59delinsHisAsn Pathogenic ★ same residue
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

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-gln58pro (accessed [today's date]).

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