Is LDLR p.Asn591= (c.1773C>T) pathogenic?

LDLR p.Asn591= (c.1773C>T) is classified Benign/Likely benign in LDLR (ClinVar, Multiple submitters, 24 submitters; last evaluated 2026-02-04). Common (popmax 44.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Asn591= (c.1773C>T)?

LDLR p.Asn591= (c.1773C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

LDLR p.Asn591=

Q: How common is LDLR p.Asn591= (c.1773C>T) in the general population?

LDLR p.Asn591= (c.1773C>T) is common (popmax 44.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1773C>T · rs688 · VCV200917

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 24 submitters

gnomAD v4.1

Common

common (popmax 44.7%, mid) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -5
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 44.7% Middle Eastern · 2,705/6,052 alleles

Filtering AF 44.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 44.5%

Overall 41.7% 673,211/1,613,584 alleles · common exomes 622,001/1,461,646 · genomes 51,210/151,938 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	47.5%	2
Middle Easterngrpmax	44.7%	2
European (non-Finnish)	44.6%	2
Ashkenazi Jewishnot grpmax-eligible	43.3%	2
Admixed American	42%	2
Remaining individualsnot grpmax-eligible	40.6%	2
South Asian	39.3%	3
Amishnot grpmax-eligible	34.9%	3
East Asian	15%	7
African / African-American	10.2%	10

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn591=
Coding: c.1773C>T
MANE Select: NM_000527
dbSNP: rs688
Type: single nucleotide variant
Location: chr19:11116926 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB

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.Asn591Asp Uncertain significance ★★ ⚠ same residue
LDLR p.Asn591Ser Uncertain significance ★ ⚠ same residue
LDLR p.Asn591fs Pathogenic ★ same residue
LDLR p.Asn591_Gly592delinsLys Conflicting classifications of pathogenicity ★ 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-asn591 (accessed [today's date]).

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