Is LDLR p.Asp172fs (c.513del) pathogenic?

LDLR p.Asp172fs (c.513del) is classified Pathogenic in LDLR (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-08-04). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Asp172fs (c.513del)?

LDLR p.Asp172fs (c.513del) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Asp172fs (c.513del) in the general population?

LDLR p.Asp172fs (c.513del) is very rare (popmax 0.00223%, eas) (gnomAD).

LDLR p.Asp172fs

c.513del · rs879254552 · VCV251264

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Cardiovascular phenotype

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 11	GERP 2.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,804 alleles · very rare exomes 3/1,461,704 · genomes 0/152,100 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
European (non-Finnish)	0.00017%	589,971

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: LDLR
Protein: p.Asp172fs
Coding: c.513del
MANE Select: NM_000527
dbSNP: rs879254552
Type: Deletion
Location: chr19:11105416 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 172: a UniProt-annotated variant site (may contribute to familial hypercholesterolemia); a UniProt-annotated variant site (in fhcl1; does not affect receptor expression at the cell surface; results in reduced ldl binding; results in reduced ldl uptake and internalization); the 'binding to getah virus e1-e2 spike glycoproteins' region; the ldl-receptor class a 4 domain

Full LDLR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia hypercholesterolemia, familial, 1

Similar variants

LDLR p.Asp172Ala Likely pathogenic ★★ same residue
LDLR p.Asp172Asn Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Asp172Glu Likely pathogenic ★★ ⚠ same residue
LDLR p.Asp172Gly Likely pathogenic ★★ same residue
LDLR p.Asp172His Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Asp172Tyr Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Asp172Val Likely pathogenic ★ same residue
LDLR p.Ala612fs 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-asp172fs (accessed [today's date]).

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