PLTP p.Leu75=
c.225G>A · rs772838662 · VCV3049751
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00466%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.35 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP 0.8, phastCons 1 |
| Overall | ||
| CADD | 17.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00466%
European (non-Finnish) · 55/1,179,966 alleles
Filtering AF
0.00367%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00329%
Overall
0.00366%
59/1,613,916 alleles · very rare
exomes 55/1,461,722 · genomes 4/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00466% | 21,454 |
| African / African-American | 0.004% | 24,976 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
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
- PLTP
- Protein
- p.Leu75=
- Coding
- c.225G>A
- MANE Select
- NM_006227
- dbSNP
- rs772838662
- Type
- single nucleotide variant
- Location
- chr20:45910046 (GRCh38)
- Gene constraint
- LOEUF 1.002 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.36
Similar variants
- PLTP p.Ala155Thr Uncertain significance ★★ ⚠ same type
- PLTP p.Ala155Val Uncertain significance ★★ ⚠ same type
- PLTP p.Arg177Cys Uncertain significance ★★ ⚠ same type
- PLTP p.Arg251Gln Uncertain significance ★★ ⚠ same type
- PLTP p.Arg372His Uncertain significance ★★ ⚠ same type
- PLTP p.Arg380Gln Uncertain significance ★★ ⚠ same type
- PLTP p.Arg391Cys Uncertain significance ★★ ⚠ same type
- PLTP p.Arg394Pro 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/pltp-p-leu75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown