Is CGB1 p.Pro96Ala (c.286C>G) pathogenic?

CGB1 p.Pro96Ala (c.286C>G) is classified Uncertain significance in CGB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). Absent from gnomAD v4.1.

How common is CGB1 p.Pro96Ala (c.286C>G) in the general population?

CGB1 p.Pro96Ala (c.286C>G) is absent from gnomAD v4.1 (gnomAD).

CGB1 p.Pro96Ala

c.286C>G · VCV4001916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.432	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 208 bp · p 8.6e-06 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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: CGB1
Protein: p.Pro96Ala
Coding: c.286C>G
MANE Select: NM_033377
Type: single nucleotide variant
Location: chr19:49035792 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 74.53
Residue 96: a disulfide bond

Full CGB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CGB1 p.Ala103Ser Uncertain significance ★ same type
CGB1 p.Ala141Val Uncertain significance ★ same type
CGB1 p.Ala18Thr Uncertain significance ★ same type
CGB1 p.Ala35Val Uncertain significance ★ same type
CGB1 p.Arg113His Uncertain significance ★ same type
CGB1 p.Arg151His Uncertain significance ★ same type
CGB1 p.Arg151Leu Uncertain significance ★ same type
CGB1 p.Arg151Pro Uncertain significance ★ 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/cgb1-p-pro96ala (accessed [today's date]).

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