PLCB4 p.Ala476=
c.1428T>C · rs140773788 · VCV339562
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.381%, afr)
Conditions
1
auriculocondylar syndrome 2
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 0.45 | GERP -0.12, phastCons 1 |
| Overall | ||
| CADD | 12.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.381%
African / African-American · 286/75,032 alleles
Filtering AF
0.345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.331%
Overall
0.0188%
303/1,613,498 alleles · rare
exomes 143/1,461,172 · genomes 160/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.381% | 262 |
| Admixed American | 0.0133% | 7,502 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,924 |
| European (non-Finnish) | 0.00017% | 589,762 |
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.Ala476=
- Coding
- c.1428T>C
- MANE Select
- NM_001377142
- dbSNP
- rs140773788
- Type
- single nucleotide variant
- Location
- chr20:9395536 (GRCh38)
- Gene constraint
- LOEUF 0.509 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 86.03
Similar variants
- PLCB4 p.Arg633Cys Pathogenic ★★ same condition
- PLCB4 p.Arg633His Pathogenic ★★ same condition
- PLCB4 p.Asp642Asn Pathogenic/Likely pathogenic ★★ same condition
- PLCB4 c.1323+8T>C Uncertain significance ★★ same condition
- PLCB4 c.*586C>T Uncertain significance ★★ same condition
- PLCB4 p.Met965Thr Uncertain significance ★★ ⚠ same condition
- PLCB4 c.1065-8A>G Benign ★★ same condition
- PLCB4 c.1611+12C>T Likely benign ★★ 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/plcb4-p-ala476 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown