LIPH p.Leu433=
c.1297C>T · rs371600390 · VCV2170244
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
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 4 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 8.293 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,866 alleles
Filtering AF
0.00188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.00205%
33/1,613,578 alleles · very rare
exomes 28/1,461,500 · genomes 5/152,078 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,433 |
| European (non-Finnish) | 0.00263% | 38,055 |
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.Leu433=
- Coding
- c.1297C>T
- MANE Select
- NM_139248
- dbSNP
- rs371600390
- Type
- single nucleotide variant
- Location
- chr3:185508849 (GRCh38)
- Gene constraint
- LOEUF 0.811 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.89
- Residue 433
- a UniProt-annotated variant site (in arwh2)
Similar variants
- LIPH p.Arg110Ter Pathogenic/Likely pathogenic ★★ same type
- LIPH p.Cys246Ser Pathogenic/Likely pathogenic ★★ same type
- LIPH p.His248Asn Pathogenic/Likely pathogenic ★★ same type
- LIPH p.Ala180Gly Uncertain significance ★★ ⚠ same type
- LIPH p.Arg110Leu Uncertain significance ★★ ⚠ same type
- LIPH p.Ile336Met Uncertain significance ★★ ⚠ same type
- LIPH p.Thr286Met Uncertain significance ★★ ⚠ same type
- LIPH c.1094+29C>T 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/liph-p-leu433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown