PLCE1 p.Ser1406=
c.4218G>A · rs537485354 · VCV2181824
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0286%, sas)
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 -0.063 | GERP -2.9, phastCons 0.012 |
| Overall | ||
| CADD | 8.677 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0286%
South Asian · 26/91,056 alleles
Filtering AF
0.0199%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0171%
Overall
0.00297%
48/1,613,902 alleles · ultra-rare
exomes 42/1,461,760 · genomes 6/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0286% | 3,502 |
| African / African-American | 0.008% | 12,498 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,833 |
| East Asian | 0.00446% | 22,429 |
| Admixed American | 0.00167% | 60,002 |
| European (non-Finnish) | 0.000848% | 117,992 |
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
- PLCE1
- Protein
- p.Ser1406=
- Coding
- c.4218G>A
- MANE Select
- NM_016341
- dbSNP
- rs537485354
- Type
- single nucleotide variant
- Location
- chr10:94265895 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.01 · 3 PDB
- Residue 1406
- the pi-plc x-box domain; a UniProt-annotated variant site (in nphs3)
Similar variants
- PLCE1 p.Ser1406Leu Uncertain significance ★ ⚠ same residue
- PLCE1 c.4506+1G>A Likely pathogenic ★★ same type
- PLCE1 c.6132+1G>A Likely pathogenic ★★ same type
- PLCE1 p.Arg1246Ter Pathogenic ★★ same type
- PLCE1 p.Arg1434Gln Likely pathogenic ★★ same type
- PLCE1 p.Arg1495Ter Pathogenic/Likely pathogenic ★★ same type
- PLCE1 p.Arg321Ter Pathogenic ★★ same type
- PLCE1 p.Arg493Ter Pathogenic ★★ 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/plce1-p-ser1406 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown