Is LDLR p.Asp47= (c.141T>C) pathogenic?

LDLR p.Asp47= (c.141T>C) is classified Likely benign in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). Very rare (popmax 0.00167%, amr); Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Asp47= (c.141T>C)?

LDLR p.Asp47= (c.141T>C) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Asp47= (c.141T>C) in the general population?

LDLR p.Asp47= (c.141T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

LDLR p.Asp47=

c.141T>C · VCV3386978

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

hypercholesterolemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -4.8
Overall
CADD	0.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Overall 6.2e-05% 1/1,613,986 alleles · very rare exomes 1/1,461,676 · genomes 0/152,310 · joint denominator

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.Asp47=
Coding: c.141T>C
MANE Select: NM_000527
Type: single nucleotide variant
Location: chr19:11100296 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 47: a β-strand; the ldl-receptor class a 1 domain; a UniProt-annotated variant site (in fhcl1; cape town-1; retards receptor transport from the endoplasmic reticulum to the cell surface)

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.Asp47Asn Uncertain significance ★★★ ⚠ same residue
LDLR p.Asp47His Uncertain significance ★★★ ⚠ same residue
LDLR p.Asp47Tyr Uncertain significance ★★★ ⚠ same residue
LDLR p.Asp47_Gly48del Likely pathogenic ★★ same residue
LDLR p.Asp47fs Pathogenic ★ same residue
LDLR p.Asp47Glu Uncertain significance ★ ⚠ same residue
LDLR c.1186+5G>A Likely pathogenic ★★★ same condition
LDLR c.1359-1G>A 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-asp47 (accessed [today's date]).

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