Is CGB2 p.Arg26Trp (c.76C>T) pathogenic?

CGB2 p.Arg26Trp (c.76C>T) is classified Uncertain significance in CGB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.1009); Rare (popmax 0.532%, afr).

How common is CGB2 p.Arg26Trp (c.76C>T) in the general population?

CGB2 p.Arg26Trp (c.76C>T) is rare (popmax 0.532%, afr) (gnomAD).

What do computational predictors say about CGB2 p.Arg26Trp (c.76C>T)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

CGB2 p.Arg26Trp

c.76C>T · rs753143101 · VCV3143880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.532%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -8.48	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 0.42	phastCons 0.003
Regional constraint	o/e 0.31	constrained · MANE · 1,053 bp · p 4.5e-22 · regional, not allelic
Overall
CADD	14.91	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 0.532% African / African-American · 366/68,744 alleles

Filtering AF 0.487% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.47%

Overall 0.0303% 465/1,536,682 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.532%	188
Remaining individualsnot grpmax-eligible	0.0617%	1,622
Admixed American	0.038%	2,634
South Asian	0.0175%	5,719
European (non-Finnish)	0.00235%	42,508

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.Arg26Trp
Coding: c.76C>T
MANE Select: NM_033378
dbSNP: rs753143101
Type: single nucleotide variant
Location: chr19:49032570 (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.Arg26Gln Uncertain significance ★ ⚠ same residue
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.Arg78Gly Uncertain significance ★ ⚠ same type
CGB2 p.Arg81His Uncertain significance ★ ⚠ same type
CGB2 p.Arg92Cys 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-arg26trp (accessed [today's date]).

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