Is LDLR p.Cys255Arg (c.762_763inv) pathogenic?

LDLR p.Cys255Arg (c.762763inv) is classified Likely pathogenic in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-25). Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Cys255Arg (c.762_763inv)?

LDLR p.Cys255Arg (c.762_763inv) is associated with hypercholesterolemia, familial, 1 (ClinVar).

LDLR p.Cys255Arg

c.762_763inv · VCV251438

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

hypercholesterolemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.5	GERP 1.9, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 42 kb · p 0.91 · regional, not allelic

Variant & gene context

Gene: LDLR
Protein: p.Cys255Arg
Coding: c.762_763inv
MANE Select: NM_000527
Type: Inversion
Location: chr19:11106632 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 255: the ldl-receptor class a 6 domain; a UniProt-annotated variant site (in fhcl1); a β-strand; a disulfide bond

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

Disease context

hypercholesterolemia, familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDLR p.Cys255Ser Likely pathogenic ★★ same residue
LDLR p.Cys255Tyr Likely pathogenic ★ same residue
LDLR p.Cys255Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Cys255Phe Pathogenic same residue
LDLR c.1186+5G>A Likely pathogenic ★★★ same condition
LDLR c.1359-1G>A Pathogenic ★★★ same condition
LDLR c.1359-5C>G Likely pathogenic ★★★ same condition
LDLR c.1705+2T>C 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-cys255arg (accessed [today's date]).

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