LDLR p.Val800fs
c.2397_2412del · rs879255197 · VCV252321
ClinGen expert panel — Familial Hypercholesterolemia VCEP
Likely Pathogenic for hypercholesterolemia, familial. Applied ACMG criteria (verbatim):
PM2 PVS1
Curation rationale (ClinGen, verbatim)
NM_000527.5(LDLR):c.2397_2412del (p.Val800fs) variant is classified as Likely Pathogenic, for Familial Hypercholesterolemia by applying evidence code PM2 and PVS1 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: . PM2: This variant is absent from gnomAD (gnomAD v2.1.1). . PSV1: Deletion of 16 bp causing an out-of-frame consequence (Exon 17)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 17 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.5, phastCons 0.99 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- LDLR
- Protein
- p.Val800fs
- Coding
- c.2397_2412del
- MANE Select
- NM_000527
- dbSNP
- rs879255197
- Type
- Deletion
- Location
- chr19:11129520 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 36 PDB
- Residue 800
- a UniProt-annotated variant site (in fhcl1)
Similar variants
- LDLR p.Val800_Leu802del Conflicting classifications of pathogenicity ★ same residue
- LDLR p.Val800Ile Benign/Likely benign ★★ same residue
- LDLR p.Val800Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
- LDLR p.Ala612fs Likely pathogenic ★★★ same condition
- LDLR p.Lys816fs Likely pathogenic ★★★ same condition
- LDLR p.Tyr400_Phe402del Likely pathogenic ★★★ same condition
- LDLR p.Phe86_Arg88del Uncertain significance ★★★ same condition
- LDLR c.1056_1060+3del Pathogenic/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/ldlr-p-val800fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown