PLCB4 p.Tyr331=
c.993T>C · VCV4944335
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.131%, mid)
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 2.9 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 7.643 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.131%
Middle Eastern · 8/6,084 alleles
Filtering AF
0.0654%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0477%
Overall
0.00254%
41/1,614,068 alleles · rare
exomes 39/1,461,854 · genomes 2/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.131% | 761 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| European (non-Finnish) | 0.00246% | 40,690 |
| Admixed American | 0.00167% | 60,002 |
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.Tyr331=
- Coding
- c.993T>C
- MANE Select
- NM_001377142
- Type
- single nucleotide variant
- Location
- chr20:9384340 (GRCh38)
- Gene constraint
- LOEUF 0.509 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 86.03
- Residue 331
- the pi-plc x-box domain
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-tyr331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown