LIPE p.Pro754=
c.2262G>A · rs28657829 · VCV778845
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.07%, afr) — too common for a highly-penetrant pathogenic allele
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 -12 | |
| Overall | ||
| CADD | 1.574 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.07%
African / African-American · 4,548/74,984 alleles
Filtering AF
5.92%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.86%
Overall
0.373%
6,017/1,613,794 alleles · common
exomes 3,487/1,461,610 · genomes 2,530/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.07% | 16 |
| Middle Eastern | 1.86% | 54 |
| Remaining individualsnot grpmax-eligible | 0.608% | 164 |
| Admixed American | 0.472% | 212 |
| Ashkenazi Jewishnot grpmax-eligible | 0.132% | 759 |
| European (non-Finnish) | 0.0526% | 1,900 |
| South Asian | 0.0329% | 3,036 |
| East Asian | 0.00669% | 14,955 |
| Finnishnot grpmax-eligible | 0.00156% | 63,944 |
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
- LIPE
- Protein
- p.Pro754=
- Coding
- c.2262G>A
- MANE Select
- NM_005357
- dbSNP
- rs28657829
- Type
- single nucleotide variant
- Location
- chr19:42406264 (GRCh38)
- Gene constraint
- LOEUF 0.932 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.77 · 1 PDB
Similar variants
- LIPE p.Arg305Cys Uncertain significance ★★ ⚠ same type
- LIPE p.Arg821Cys Uncertain significance ★★ ⚠ same type
- LIPE p.Gln150Glu Uncertain significance ★★ ⚠ same type
- LIPE p.Leu1027Met Uncertain significance ★★ ⚠ same type
- LIPE p.Leu777Phe Uncertain significance ★★ ⚠ same type
- LIPE p.Val1014Met Uncertain significance ★★ ⚠ same type
- LIPE c.2365+181T>A Benign ★★ same type
- LIPE c.2968-44C>G Benign ★★ 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/lipe-p-pro754 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown