Is LDLR p.Ser252fs (c.752dup) pathogenic?

LDLR p.Ser252fs (c.752dup) is classified Pathogenic in LDLR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-05-04). Absent from gnomAD; Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Ser252fs (c.752dup)?

LDLR p.Ser252fs (c.752dup) is associated with familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Ser252fs (c.752dup) in the general population?

LDLR p.Ser252fs (c.752dup) is absent from gnomAD (gnomAD).

LDLR p.Ser252fs

c.752dup · rs879254666 · VCV251434

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 5 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -13	GERP -3.7

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

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.Ser252fs
Coding: c.752dup
MANE Select: NM_000527
dbSNP: rs879254666
Type: Duplication
Location: chr19:11106620 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 252: the ldl-receptor class a 6 domain; an α-helix; a disulfide bond

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

Also linked: hypercholesterolemia, familial, 1

Similar variants

LDLR p.Glu763fs Likely pathogenic ★★★ same condition
LDLR p.Cys803_Leu808dup Uncertain significance ★★★ same condition
LDLR c.313+1dup Pathogenic/Likely pathogenic ★★ same condition
LDLR c.313+2dup Pathogenic/Likely pathogenic ★★ same condition
LDLR c.314-446_1187-386dup Pathogenic/Likely pathogenic ★★ same condition
LDLR p.Ala13fs Pathogenic ★★ same condition
LDLR p.Ala151fs Pathogenic ★★ same condition
LDLR p.Ala459fs 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-ser252fs (accessed [today's date]).

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