Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.7%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.14 | GERP -4.8, phastCons 0.054 |
| Overall | ||
| CADD | 2.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.7%
African / African-American · 3,522/74,964 alleles
Filtering AF
4.57%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.52%
Overall
0.264%
4,253/1,612,992 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.7% | 21 |
| Middle Eastern | 0.925% | 108 |
| Remaining individualsnot grpmax-eligible | 0.443% | 225 |
| Admixed American | 0.367% | 272 |
| South Asian | 0.0253% | 3,951 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0203% | 4,928 |
| European (non-Finnish) | 0.0124% | 8,079 |
| East Asian | 0.00446% | 22,398 |
| Finnishnot grpmax-eligible | 0.00156% | 63,966 |
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
- PLCB1
- Protein
- p.Val733=
- Coding
- c.2199G>A
- MANE Select
- NM_015192
- dbSNP
- rs8118206
- Type
- single nucleotide variant
- Location
- chr20:8737183 (GRCh38)
- Gene constraint
- LOEUF 0.357 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.55
- Residue 733
- the c2 domain
Similar variants
- PLCB1 p.Arg222Ter Pathogenic/Likely pathogenic ★★ same condition
- PLCB1 p.Arg815Ter Pathogenic/Likely pathogenic ★★ same condition
- PLCB1 c.3336+3A>G Uncertain significance ★★ same condition
- PLCB1 p.Ala1046Ser Uncertain significance ★★ ⚠ same condition
- PLCB1 p.Ala1046Thr Uncertain significance ★★ ⚠ same condition
- PLCB1 p.Ala1116Val Uncertain significance ★★ ⚠ same condition
- PLCB1 p.Ala1182Val Uncertain significance ★★ ⚠ same condition
- PLCB1 p.Ala155Val Uncertain significance ★★ ⚠ same condition
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/plcb1-p-val733 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown