Is CGB1 p.Cys27Phe (c.80G>T) pathogenic?

CGB1 p.Cys27Phe (c.80G>T) is classified Uncertain significance in CGB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). Ultra-rare (popmax 0.0214%, mid).

How common is CGB1 p.Cys27Phe (c.80G>T) in the general population?

CGB1 p.Cys27Phe (c.80G>T) is ultra-rare (popmax 0.0214%, mid) (gnomAD).

CGB1 p.Cys27Phe

c.80G>T · VCV4653078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0214%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.599	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	phastCons 1
Regional constraint	o/e 0.20	constrained · MANE · 346 bp · p 4e-09 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0214% Middle Eastern · 1/4,664 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00217% 35/1,609,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0214%	4,664
European (non-Finnish)	0.0028%	35,749
Remaining individualsnot grpmax-eligible	0.00161%	62,294

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.Cys27Phe
Coding: c.80G>T
MANE Select: NM_033377
Type: single nucleotide variant
Location: chr19:49036233 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 74.53

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-cys27phe (accessed [today's date]).

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