PLCB4 p.Ser70=
c.210G>A · VCV3712870
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00501%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP -0.39, phastCons 1 |
| Overall | ||
| CADD | 13.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00501%
Admixed American · 3/59,896 alleles
Filtering AF
0.00189%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.0023%
37/1,610,378 alleles · very rare
exomes 29/1,458,320 · genomes 8/152,058 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00501% | 19,965 |
| African / African-American | 0.00267% | 37,397 |
| European (non-Finnish) | 0.00263% | 37,970 |
| East Asian | 0.00223% | 44,812 |
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
- PLCB4
- Protein
- p.Ser70=
- Coding
- c.210G>A
- MANE Select
- NM_001377142
- Type
- single nucleotide variant
- Location
- chr20:9338052 (GRCh38)
- Gene constraint
- LOEUF 0.509 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 86.03
Similar variants
- PLCB4 p.Arg633Cys Pathogenic ★★ same type
- PLCB4 p.Arg633His Pathogenic ★★ same type
- PLCB4 p.Asp642Asn Pathogenic/Likely pathogenic ★★ same type
- PLCB4 c.1323+8T>C Uncertain significance ★★ same type
- PLCB4 c.*586C>T Uncertain significance ★★ same type
- PLCB4 p.Arg640Gln Uncertain significance ★★ ⚠ same type
- PLCB4 p.Glu1005Lys Uncertain significance ★★ ⚠ same type
- PLCB4 p.Met965Thr 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/plcb4-p-ser70 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown