CGB1 p.Pro42Ala
c.124C>G · rs755513430 · VCV3143871
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.242 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | phastCons 1 |
| Regional constraint | o/e 0.20 | constrained · MANE · 346 bp · p 4e-09 · regional, not allelic |
| Overall | ||
| CADD | 21.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/59,978 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00579%
Overall
0.00118%
19/1,609,930 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.015% | 6,664 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,152 |
| African / African-American | 0.00268% | 37,378 |
| European (non-Finnish) | 0.000509% | 196,634 |
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.Pro42Ala
- Coding
- c.124C>G
- MANE Select
- NM_033377
- dbSNP
- rs755513430
- Type
- single nucleotide variant
- Location
- chr19:49036189 (GRCh38)
- Gene constraint
- LOEUF 1.532 · pLI 0.11 (gnomAD)
- Structure
- AlphaFold pLDDT 74.53
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-pro42ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown