Is PCCB p.Pro103Leu (c.308C>T) pathogenic?

PCCB p.Pro103Leu (c.308C>T) is classified Uncertain significance in PCCB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.1214); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PCCB p.Pro103Leu (c.308C>T)?

PCCB p.Pro103Leu (c.308C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCCB p.Pro103Leu (c.308C>T) in the general population?

PCCB p.Pro103Leu (c.308C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCCB p.Pro103Leu (c.308C>T)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

PCCB p.Pro103Leu

c.308C>T · VCV3928476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -9.36	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 80 kb · p 0.017 · regional, not allelic
Overall
CADD	28.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PCCB
Protein: p.Pro103Leu
Coding: c.308C>T
MANE Select: NM_000532
Type: single nucleotide variant
Location: chr3:136256559 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.59 · 24 PDB
Residue 103: the coa carboxyltransferase n-terminal domain; the 'carboxyltransferase' region

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

Similar variants

PCCB c.1499-1G>C Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Arg512Cys Pathogenic ★★ same condition
PCCB p.Tyr314Ter Pathogenic/Likely pathogenic ★★ same condition
PCCB p.Ala148Gly Uncertain significance ★★ ⚠ same condition
PCCB p.Ala257Thr Uncertain significance ★★ ⚠ same condition
PCCB p.Ala3Val Uncertain significance ★★ ⚠ same condition
PCCB p.Arg289His Uncertain significance ★★ ⚠ same condition
PCCB p.Arg297His Uncertain significance ★★ ⚠ 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-pro103leu (accessed [today's date]).

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