Is CGB1 p.Pro91Arg (c.272C>G) pathogenic?

CGB1 p.Pro91Arg (c.272C>G) is classified Uncertain significance in CGB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). Very rare (popmax 0.00206%, nfe).

How common is CGB1 p.Pro91Arg (c.272C>G) in the general population?

CGB1 p.Pro91Arg (c.272C>G) is very rare (popmax 0.00206%, nfe) (gnomAD).

CGB1 p.Pro91Arg

c.272C>G · VCV4001910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00206%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.43	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 208 bp · p 8.6e-06 · regional, not allelic
Overall
CADD	12.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00206% European (non-Finnish) · 24/1,164,450 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00117%

Overall 0.00181% 26/1,436,862 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00327%	30,586
European (non-Finnish)grpmax	0.00206%	48,519

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CGB1
Protein: p.Pro91Arg
Coding: c.272C>G
MANE Select: NM_033377
Type: single nucleotide variant
Location: chr19:49035806 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 74.53
Residue 91: a disulfide bond

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

Similar variants

CGB1 p.Pro91Leu Uncertain significance ★ same residue
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

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-pro91arg (accessed [today's date]).

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