Is LDLR p.Asp90= (c.270T>C) pathogenic?

LDLR p.Asp90= (c.270T>C) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Asp90= (c.270T>C)?

LDLR p.Asp90= (c.270T>C) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Asp90= (c.270T>C) in the general population?

LDLR p.Asp90= (c.270T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

LDLR p.Asp90=

c.270T>C · rs372828849 · VCV413775

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Cardiovascular phenotype

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 -14	GERP -5.1
Overall
CADD	0.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.00031% 5/1,614,014 alleles · ultra-rare exomes 3/1,461,726 · genomes 2/152,288 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,249
Admixed American	0.00167%	59,994
European (non-Finnish)	8.48e-05%	1,179,928

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.Asp90=
Coding: c.270T>C
MANE Select: NM_000527
dbSNP: rs372828849
Type: single nucleotide variant
Location: chr19:11102743 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 90: a β-strand; the ldl-receptor class a 2 domain; a UniProt-annotated variant site (in fhcl1; pathogenic; london-4); a UniProt-annotated variant site (in fhcl1; pathogenic); a UniProt-annotated variant site (in fhcl1; likely pathogenic; durban-1)

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.Asp90Ala Likely pathogenic ★★★ same residue
LDLR p.Asp90Asn Pathogenic ★★★ ⚠ same residue
LDLR p.Asp90Glu Pathogenic ★★★ same residue
LDLR p.Asp90Gly Pathogenic ★★★ same residue
LDLR p.Asp90Tyr Likely pathogenic ★★★ 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

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-asp90 (accessed [today's date]).

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