LIPE p.Ala1040=
c.3120A>G · VCV4942736
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.12%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | |
| Overall | ||
| CADD | 0.215 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.12%
East Asian · 888/41,956 alleles
Filtering AF
2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.95%
Overall
0.058%
901/1,553,990 alleles · low-frequency
exomes 867/1,402,330 · genomes 34/151,660 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 2.12% | 47 |
| Remaining individualsnot grpmax-eligible | 0.0199% | 5,029 |
| Admixed American | 0.00191% | 52,222 |
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.Ala1040=
- Coding
- c.3120A>G
- MANE Select
- NM_005357
- Type
- single nucleotide variant
- Location
- chr19:42401923 (GRCh38)
- Gene constraint
- LOEUF 0.932 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.77 · 1 PDB
- Residue 1040
- an α-helix
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-ala1040 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown