Is LDLR p.Cys352del (c.1054_1056del) pathogenic?

LDLR p.Cys352del (c.10541056del) is classified Likely pathogenic in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-01). No gnomAD frequency available for this variant; Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Cys352del (c.1054_1056del)?

LDLR p.Cys352del (c.1054_1056del) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Cys352del (c.1054_1056del) in the general population?

LDLR p.Cys352del (c.1054_1056del) is no gnomAD frequency available for this variant (gnomAD).

LDLR p.Cys352del

c.1054_1056del · rs2077364374 · VCV982979

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 0.02	GERP -4.9

Population frequency

dbSNP / gnomAD

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.Cys352del
Coding: c.1054_1056del
MANE Select: NM_000527
dbSNP: rs2077364374
Type: Deletion
Location: chr19:11110765 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 352: the egf-like 1 domain; a UniProt-annotated variant site (in fhcl1; uncertain significance); a UniProt-annotated variant site (in fhcl1; likely pathogenic; mexico-2); 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.Cys352fs Pathogenic ★ same residue
LDLR p.Cys352Tyr Likely pathogenic ★★★ same residue
LDLR p.Cys352= Benign ★★★ same residue
LDLR p.Cys352Arg Likely pathogenic ★★ same residue
LDLR p.Cys352Phe Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Cys352Ser Likely pathogenic ★★ same residue
LDLR p.Cys352Ter Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Cys352Trp Pathogenic/Likely pathogenic ★★ same residue

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-cys352del (accessed [today's date]).

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