LIPE p.His663=
c.1989C>T · rs371656191 · VCV731850
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0424%, 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 -11 | |
| Overall | ||
| CADD | 0.206 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0424%
East Asian · 19/44,822 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.023%
Overall
0.00217%
35/1,612,108 alleles · ultra-rare
exomes 33/1,459,882 · genomes 2/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0424% | 2,359 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,930 |
| South Asian | 0.0011% | 90,786 |
| European (non-Finnish) | 0.000509% | 196,546 |
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.His663=
- Coding
- c.1989C>T
- MANE Select
- NM_005357
- dbSNP
- rs371656191
- Type
- single nucleotide variant
- Location
- chr19:42407322 (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-his663 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown