Is LDLR p.Arg508fs (c.1522delinsCTGAAT) pathogenic?

LDLR p.Arg508fs (c.1522delinsCTGAAT) is classified Pathogenic in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-25). No gnomAD frequency available for this variant; Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Arg508fs (c.1522delinsCTGAAT)?

LDLR p.Arg508fs (c.1522delinsCTGAAT) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Arg508fs (c.1522delinsCTGAAT) in the general population?

LDLR p.Arg508fs (c.1522delinsCTGAAT) is no gnomAD frequency available for this variant (gnomAD).

LDLR p.Arg508fs

c.1522delinsCTGAAT · rs879254930 · VCV251884

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 0.44, phastCons 1

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.Arg508fs
Coding: c.1522delinsCTGAAT
MANE Select: NM_000527
dbSNP: rs879254930
Type: Indel
Location: chr19:11113698 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 508: a β-strand

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 c.1359-31_1359-23delinsCGGCT Uncertain significance ★★★ same condition
LDLR p.Arg257His Uncertain significance ★★★ same condition
LDLR p.Arg744Gln Uncertain significance ★★★ same condition
LDLR p.Asp224_Lys225delinsPhe Uncertain significance ★★★ same condition
LDLR p.Val653Ala Uncertain significance ★★★ same condition
LDLR c.191-2delinsCT Pathogenic/Likely pathogenic ★★ same condition
LDLR c.313_313+1delinsTC Likely pathogenic ★★ same condition
LDLR p.? 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-arg508fs (accessed [today's date]).

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