Is LDLR p.Ser499fs (c.1496_1497del) pathogenic?

LDLR p.Ser499fs (c.14961497del) is classified Pathogenic/Likely pathogenic in LDLR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-01-02). No gnomAD frequency available for this variant; Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Ser499fs (c.1496_1497del)?

LDLR p.Ser499fs (c.1496_1497del) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Ser499fs (c.1496_1497del) in the general population?

LDLR p.Ser499fs (c.1496_1497del) is no gnomAD frequency available for this variant (gnomAD).

LDLR p.Ser499fs

c.1496_1497del · rs879254922 · VCV251871

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely 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

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 2.1	GERP -5.1, phastCons 0.98

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.Ser499fs
Coding: c.1496_1497del
MANE Select: NM_000527
dbSNP: rs879254922
Type: Microsatellite
Location: chr19:11113669 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 499: 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 p.Ser499Pro Likely pathogenic ★★★ same residue
LDLR p.Ser499Cys Uncertain significance ★★★ ⚠ same residue
LDLR p.Gly219del Pathogenic ★★★ same condition
LDLR p.Phe403del Likely pathogenic ★★★ same condition
LDLR c.190+2_190+3del Likely pathogenic ★★ same condition
LDLR p.Arg124fs Pathogenic ★★ same condition
LDLR p.Arg458fs Pathogenic ★★ same condition
LDLR p.Asn322del 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-ser499fs (accessed [today's date]).

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