LIPE p.Ala722=
c.2166G>A · rs371435924 · VCV1338694
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.489%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.84 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.53 | gain · loss 0.18 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -16 | |
| Overall | ||
| CADD | 17.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.489%
South Asian · 445/91,072 alleles
Filtering AF
0.451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.436%
Overall
0.0378%
610/1,613,806 alleles · rare
exomes 564/1,461,496 · genomes 46/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.489% | 205 |
| Ashkenazi Jewishnot grpmax-eligible | 0.182% | 548 |
| Remaining individualsnot grpmax-eligible | 0.0544% | 1,838 |
| Middle Eastern | 0.0495% | 2,021 |
| Admixed American | 0.025% | 4,002 |
| African / African-American | 0.016% | 6,252 |
| European (non-Finnish) | 0.0039% | 25,646 |
| East Asian | 0.00223% | 44,870 |
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.Ala722=
- Coding
- c.2166G>A
- MANE Select
- NM_005357
- dbSNP
- rs371435924
- Type
- single nucleotide variant
- Location
- chr19:42406360 (GRCh38)
- Gene constraint
- LOEUF 0.932 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.77 · 1 PDB
Similar variants
- LIPE p.Ala722Val Uncertain significance ★ ⚠ same residue
- 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
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-ala722 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown