Is LDLR p.Glu101= (c.303G>A) pathogenic?

LDLR p.Glu101= (c.303G>A) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-29). Very rare (popmax 0.00017%, nfe); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Glu101= (c.303G>A)?

LDLR p.Glu101= (c.303G>A) is associated with familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Glu101= (c.303G>A) in the general population?

LDLR p.Glu101= (c.303G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

LDLR p.Glu101=

c.303G>A · rs1600705245 · VCV792454

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

familial hypercholesterolemia

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 1.3	GERP -5.1, phastCons 0.76
Overall
CADD	1.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,666 alleles

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

Overall 0.000137% 2/1,461,310 alleles · very rare

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.Glu101=
Coding: c.303G>A
MANE Select: NM_000527
dbSNP: rs1600705245
Type: single nucleotide variant
Location: chr19:11102776 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 101: an α-helix; a disulfide bond; the ldl-receptor class a 2 domain; a UniProt-annotated variant site (in fhcl1; pathogenic; lancashire; 6% of american english)

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

Disease context

familial hypercholesterolemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypercholesterolemia, familial, 1

Similar variants

LDLR p.Glu101Lys Pathogenic ★★★ same residue
LDLR p.Glu101Ala Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Glu101Ter Pathogenic ★★ same residue
LDLR p.Glu101Asp Uncertain significance ★ ⚠ same residue
LDLR p.Glu101fs Pathogenic ★ same residue
LDLR p.Glu101Gly Likely pathogenic ★ 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-glu101 (accessed [today's date]).

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