Is CGB2 p.Ser19Pro (c.55T>C) pathogenic?

CGB2 p.Ser19Pro (c.55T>C) is classified Uncertain significance in CGB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.0939); Very rare (popmax 0.00533%, amr).

How common is CGB2 p.Ser19Pro (c.55T>C) in the general population?

CGB2 p.Ser19Pro (c.55T>C) is very rare (popmax 0.00533%, amr) (gnomAD).

What do computational predictors say about CGB2 p.Ser19Pro (c.55T>C)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

CGB2 p.Ser19Pro

c.55T>C · rs781369789 · VCV2235471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -8.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	phastCons 0.81
Regional constraint	o/e 0.31	constrained · MANE · 1,053 bp · p 4.5e-22 · regional, not allelic
Overall
CADD	13.66	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% Admixed American · 3/56,300 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000692%

Overall 0.00134% 21/1,568,068 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00533%	18,767
Remaining individualsnot grpmax-eligible	0.00328%	30,533
African / African-American	0.00141%	70,690
European (non-Finnish)	0.0012%	83,276
South Asian	0.00112%	89,050

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: CGB2
Protein: p.Ser19Pro
Coding: c.55T>C
MANE Select: NM_033378
dbSNP: rs781369789
Type: single nucleotide variant
Location: chr19:49032549 (GRCh38)
Gene constraint: LOEUF 1.73 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 78.22

Full CGB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CGB2 p.Ala135Asp Benign ★★ same type
CGB2 p.Ala141Gly Uncertain significance ★ ⚠ same type
CGB2 p.Arg113Cys Uncertain significance ★ ⚠ same type
CGB2 p.Arg24Gln Uncertain significance ★ ⚠ same type
CGB2 p.Arg26Gln Uncertain significance ★ ⚠ same type
CGB2 p.Arg26Trp Uncertain significance ★ ⚠ same type
CGB2 p.Arg78Gly Uncertain significance ★ ⚠ same type
CGB2 p.Arg81His 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/cgb2-p-ser19pro (accessed [today's date]).

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