Is LDLR p.Asn30= (c.90C>T) pathogenic?

LDLR p.Asn30= (c.90C>T) is classified Conflicting classifications of pathogenicity in LDLR (ClinVar, Conflicting submitters, 16 submitters; last evaluated 2026-01-31). Low-frequency (popmax 3.19%, afr); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Asn30= (c.90C>T)?

LDLR p.Asn30= (c.90C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Asn30= (c.90C>T) in the general population?

LDLR p.Asn30= (c.90C>T) is low-frequency (popmax 3.19%, afr) (gnomAD).

LDLR p.Asn30=

c.90C>T · rs72658855 · VCV251012

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.19%, afr)

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 -9.1	GERP -4.8
Overall
CADD	4.142	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.19% African / African-American · 2,392/74,998 alleles

Filtering AF 3.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.04%

Overall 0.167% 2,693/1,613,462 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.19%	31
Remaining individualsnot grpmax-eligible	0.19%	525
Admixed American	0.167%	600
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.00644%	15,526
South Asian	0.0022%	45,540

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.Asn30=
Coding: c.90C>T
MANE Select: NM_000527
dbSNP: rs72658855
Type: single nucleotide variant
Location: chr19:11100245 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 30: a β-strand; the ldl-receptor class a 1 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.Asn30Lys 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
LDLR c.190+4A>T Likely pathogenic ★★★ same condition
LDLR c.2140+1G>A Pathogenic ★★★ same condition
LDLR c.2389+2T>G 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-asn30 (accessed [today's date]).

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