Is LDLR p.Ser142fs (c.424_430del) pathogenic?

LDLR p.Ser142fs (c.424430del) is classified Pathogenic in LDLR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-05-24). No gnomAD frequency available for this variant; Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Ser142fs (c.424_430del)?

LDLR p.Ser142fs (c.424_430del) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Ser142fs (c.424_430del) in the general population?

LDLR p.Ser142fs (c.424_430del) is no gnomAD frequency available for this variant (gnomAD).

LDLR p.Ser142fs

c.424_430del · rs879254521 · VCV251218

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

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 4 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 0.39, 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.Ser142fs
Coding: c.424_430del
MANE Select: NM_000527
dbSNP: rs879254521
Type: Deletion
Location: chr19:11105327 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 142: a turn; the ldl-receptor class a 3 domain

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.Ser142= Benign same residue
LDLR p.Ala612fs Likely pathogenic ★★★ same condition
LDLR p.Lys816fs Likely pathogenic ★★★ same condition
LDLR p.Tyr400_Phe402del Likely pathogenic ★★★ same condition
LDLR p.Val800fs Likely pathogenic ★★★ same condition
LDLR p.Phe86_Arg88del Uncertain significance ★★★ same condition
LDLR c.1056_1060+3del Pathogenic/Likely pathogenic ★★ same condition
LDLR c.(1060+1_1061-1 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-ser142fs (accessed [today's date]).

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