Is CGB7 p.Arg30Pro (c.89G>C) pathogenic?

CGB7 p.Arg30Pro (c.89G>C) is classified Uncertain significance in CGB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely pathogenic (0.8); Ultra-rare (popmax 0.0141%, afr).

How common is CGB7 p.Arg30Pro (c.89G>C) in the general population?

CGB7 p.Arg30Pro (c.89G>C) is ultra-rare (popmax 0.0141%, afr) (gnomAD).

What do computational predictors say about CGB7 p.Arg30Pro (c.89G>C)?

AlphaMissense predicts likely pathogenic (score 0.8) — an in-silico prediction, not a clinical call.

CGB7 p.Arg30Pro

c.89G>C · VCV4001925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8	likely pathogenic
REVEL	0.555	indeterminate
SaProt	LLR -13.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.038	phastCons 0.62
Regional constraint	o/e 0.63	unconstrained · MANE · 788 bp · p 0.00043 · regional, not allelic
Overall
CADD	19.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0141% African / African-American · 10/71,052 alleles

Filtering AF 0.00759% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00577%

Overall 0.0007% 11/1,571,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0141%	7,105
Remaining individualsnot grpmax-eligible	0.00163%	61,314

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: CGB7
Protein: p.Arg30Pro
Coding: c.89G>C
MANE Select: NM_001385261
Type: single nucleotide variant
Location: chr19:49054935 (GRCh38)
Gene constraint: LOEUF 1.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 30: a disulfide bond

Full CGB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CGB7 p.Arg30His Uncertain significance ★ ⚠ same residue
CGB7 p.Ala103Thr Uncertain significance ★ ⚠ same type
CGB7 p.Arg115His Uncertain significance ★ ⚠ same type
CGB7 p.Arg63Cys Uncertain significance ★ ⚠ same type
CGB7 p.Arg80Gly Uncertain significance ★ ⚠ same type
CGB7 p.Arg80His Uncertain significance ★ ⚠ same type
CGB7 p.Arg83Cys Uncertain significance ★ ⚠ same type
CGB7 p.Arg88Gln 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/cgb7-p-arg30pro (accessed [today's date]).

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