PLCE1 p.Arg454=
c.1362C>T · VCV4750400
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00988%, 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 -2.3 | GERP -4.1 |
| Overall | ||
| CADD | 9.136 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00988%
South Asian · 9/91,060 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00136%
22/1,613,852 alleles · very rare
exomes 17/1,461,858 · genomes 5/151,994 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00988% | 10,118 |
| African / African-American | 0.00668% | 14,974 |
| East Asian | 0.00446% | 22,434 |
| European (non-Finnish) | 0.000508% | 196,664 |
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.Arg454=
- Coding
- c.1362C>T
- MANE Select
- NM_016341
- Type
- single nucleotide variant
- Location
- chr10:94132329 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.01 · 3 PDB
Similar variants
- PLCE1 p.Arg454Gly Uncertain significance ★ ⚠ same residue
- PLCE1 p.Arg454His 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
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-arg454 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown