PLCE1 p.Ser1000=
c.3000C>T · VCV4750441
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0446%, eas)
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 -6.3 | GERP -4.3 |
| Overall | ||
| CADD | 0.752 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0446%
East Asian · 20/44,872 alleles
Filtering AF
0.0295%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0246%
Overall
0.00285%
46/1,614,024 alleles · ultra-rare
exomes 44/1,461,730 · genomes 2/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0446% | 2,244 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,248 |
| South Asian | 0.0022% | 45,535 |
| European (non-Finnish) | 0.00178% | 56,187 |
| African / African-American | 0.00133% | 75,046 |
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.Ser1000=
- Coding
- c.3000C>T
- MANE Select
- NM_016341
- Type
- single nucleotide variant
- Location
- chr10:94246525 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.01 · 3 PDB
Similar variants
- PLCE1 p.Ser1000Asn Conflicting classifications of pathogenicity ★ ⚠ 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-ser1000 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown