LIPH p.Asp300Ala
c.899A>C · rs776331827 · VCV3064369
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1031 | likely benign |
|---|---|---|
| REVEL | 0.635 | indeterminate |
| SaProt | LLR -9.88 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.92 | unconstrained · MANE · 44 kb · p 0.056 · regional, not allelic |
| Overall | ||
| CADD | 22.3 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.00324% | 30,822 |
| South Asiangrpmax | 0.00221% | 45,272 |
| European (non-Finnish) | 0.00138% | 72,338 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- LIPH
- Protein
- p.Asp300Ala
- Coding
- c.899A>C
- MANE Select
- NM_139248
- dbSNP
- rs776331827
- Type
- single nucleotide variant
- Location
- chr3:185517150 (GRCh38)
- Gene constraint
- LOEUF 0.811 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.89
- Residue 300
- a UniProt-annotated variant site (in arwh2)
Disease context
hypotrichosis 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Woolly hair (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- LIPH p.Arg110Ter Pathogenic/Likely pathogenic ★★ same condition
- LIPH p.Cys246Ser Pathogenic/Likely pathogenic ★★ same condition
- LIPH p.His248Asn Pathogenic/Likely pathogenic ★★ same condition
- LIPH p.Gly161Glu Uncertain significance ★ ⚠ same condition
- LIPH p.His205Arg Uncertain significance ★ ⚠ same condition
- LIPH p.Ile220fs Pathogenic ★★ same condition
- LIPH p.Lys123_Thr124insGlyLeuLeuSerValGluAspMetAsnValValValValAspTrpAsnArgGlyAlaThrThrLeuIleTyrThrHisAlaSerSerLys Pathogenic/Likely pathogenic ★★ same condition
- LIPH p.Asp229fs Likely pathogenic ★ same condition
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/liph-p-asp300ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown