Is LDLR p.Asp700= (c.2100C>T) pathogenic?

LDLR p.Asp700= (c.2100C>T) is classified Conflicting classifications of pathogenicity in LDLR (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-05-04). Very rare (popmax 0.00667%, amr); Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Asp700= (c.2100C>T)?

LDLR p.Asp700= (c.2100C>T) is associated with hypercholesterolemia, familial, 1, familial hypercholesterolemia (ClinVar).

How common is LDLR p.Asp700= (c.2100C>T) in the general population?

LDLR p.Asp700= (c.2100C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

LDLR p.Asp700=

c.2100C>T · rs759858813 · VCV891487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, 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 -12	GERP -5.1
Overall
CADD	0.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,012 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000558% 9/1,613,846 alleles · very rare exomes 9/1,461,518 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,003
Remaining individualsnot grpmax-eligible	0.0048%	20,836
Finnishnot grpmax-eligible	0.00157%	63,668
European (non-Finnish)	8.47e-05%	1,180,038

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.Asp700=
Coding: c.2100C>T
MANE Select: NM_000527
dbSNP: rs759858813
Type: single nucleotide variant
Location: chr19:11120482 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 700: the egf-like 3 domain; a UniProt-annotated variant site (in fhcl1; uncertain significance)

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

Also linked: familial hypercholesterolemia

Similar variants

LDLR p.Asp700Asn Likely pathogenic ★★★ ⚠ same residue
LDLR p.Asp700Gly Likely pathogenic ★★★ same residue
LDLR p.Asp700Glu Uncertain significance ★★★ ⚠ same residue
LDLR p.Asp700Val Uncertain significance ★ ⚠ same residue
LDLR c.1186+5G>A Likely pathogenic ★★★ same condition
LDLR c.1359-1G>A Pathogenic ★★★ same condition
LDLR c.1359-5C>G Likely pathogenic ★★★ same condition
LDLR c.1705+2T>C 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-asp700 (accessed [today's date]).

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