CGB1 p.Ala69Pro
c.205G>C · rs574589925 · VCV2650232
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.702%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.063 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | phastCons 1 |
| Regional constraint | o/e 0.57 | unconstrained · MANE · 208 bp · p 8.6e-06 · regional, not allelic |
| Overall | ||
| CADD | 9.332 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.702%
European (non-Finnish) · 7,501/1,068,992 alleles
Filtering AF
0.688%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.683%
Overall
0.575%
8,293/1,442,202 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.702% | 143 |
| Admixed American | 0.504% | 198 |
| Remaining individualsnot grpmax-eligible | 0.493% | 203 |
| Amishnot grpmax-eligible | 0.225% | 445 |
| South Asian | 0.161% | 620 |
| Finnishnot grpmax-eligible | 0.128% | 778 |
| African / African-American | 0.0857% | 1,166 |
| Middle Eastern | 0.0732% | 1,365 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0382% | 2,618 |
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.Ala69Pro
- Coding
- c.205G>C
- MANE Select
- NM_033377
- dbSNP
- rs574589925
- Type
- single nucleotide variant
- Location
- chr19:49035873 (GRCh38)
- Gene constraint
- LOEUF 1.532 · pLI 0.11 (gnomAD)
- Structure
- AlphaFold pLDDT 74.53
- Residue 69
- a disulfide bond
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-ala69pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown