Is LDLR p.Lys830fs (c.2487del) pathogenic?

LDLR p.Lys830fs (c.2487del) is classified Uncertain significance in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Lys830fs (c.2487del)?

LDLR p.Lys830fs (c.2487del) is associated with familial hypercholesterolemia (ClinVar).

LDLR p.Lys830fs

c.2487del · VCV4530599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

familial hypercholesterolemia

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 7.8	GERP -3.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: LDLR
Protein: p.Lys830fs
Coding: c.2487del
MANE Select: NM_000527
Type: Deletion
Location: chr19:11129610 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 830: the 'required for mylip-triggered down-regulation of ldlr' region

Full LDLR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial hypercholesterolemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDLR p.Lys830Ter Uncertain significance ★★★ same residue
LDLR p.Lys830= Likely benign ★ same residue
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
LDLR c.1187del Pathogenic ★★ same condition
LDLR c.1845+2del 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-lys830fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown