Is LDLR p.Asp579fs (c.1736_1737delinsT) pathogenic?

LDLR p.Asp579fs (c.17361737delinsT) is classified Pathogenic in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-30). No gnomAD frequency available for this variant; Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Asp579fs (c.1736_1737delinsT)?

LDLR p.Asp579fs (c.1736_1737delinsT) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Asp579fs (c.1736_1737delinsT) in the general population?

LDLR p.Asp579fs (c.1736_1737delinsT) is no gnomAD frequency available for this variant (gnomAD).

LDLR p.Asp579fs

c.1736_1737delinsT · rs1131692214 · VCV430784

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 12 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.1	GERP 1.5, 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.Asp579fs
Coding: c.1736_1737delinsT
MANE Select: NM_000527
dbSNP: rs1131692214
Type: Indel
Location: chr19:11116889 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 579: a UniProt-annotated variant site (in fhcl1; cincinnati-4; less than 2% receptor activity); a UniProt-annotated variant site (in fhcl1); 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.Asp579Gly Likely pathogenic ★★ same residue
LDLR p.Asp579Tyr Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Asp579_Ser580insLeu Pathogenic ★ same residue
LDLR p.Asp579Ala Likely pathogenic ★ same residue
LDLR p.Asp579Glu Likely pathogenic ★ ⚠ same residue
LDLR p.Asp579Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Asp579Val Pathogenic same residue
LDLR c.1359-31_1359-23delinsCGGCT Uncertain significance ★★★ 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-asp579fs (accessed [today's date]).

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