Is LDLR p.Arg471= (c.1413A>G) pathogenic?

LDLR p.Arg471= (c.1413A>G) is classified Benign in LDLR (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-02-04). Common (popmax 75.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Arg471= (c.1413A>G)?

LDLR p.Arg471= (c.1413A>G) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

LDLR p.Arg471=

Q: How common is LDLR p.Arg471= (c.1413A>G) in the general population?

LDLR p.Arg471= (c.1413A>G) is common (popmax 75.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1413A>G · rs5930 · VCV200916

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

gnomAD v4.1

Common

common (popmax 75.2%, afr) — 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 -0.031	GERP -4.1
Overall
CADD	3.718	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75.2% African / African-American · 56,382/74,966 alleles

Filtering AF 74.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 74.5%

Overall 62.1% 1,002,479/1,613,574 alleles · common exomes 902,905/1,461,586 · genomes 99,574/151,988 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	75.2%	1
Admixed American	70.6%	1
Finnishnot grpmax-eligible	63.3%	2
Ashkenazi Jewishnot grpmax-eligible	62.8%	2
Remaining individualsnot grpmax-eligible	61.8%	2
South Asian	61.3%	2
Middle Eastern	61.1%	2
European (non-Finnish)	60.9%	2
East Asian	60.9%	2
Amishnot grpmax-eligible	53%	2

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.Arg471=
Coding: c.1413A>G
MANE Select: NM_000527
dbSNP: rs5930
Type: single nucleotide variant
Location: chr19:11113589 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 471: 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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia hypercholesterolemia, familial, 1

Similar variants

LDLR p.Arg471Lys Uncertain significance ★★★ ⚠ same residue
LDLR p.Arg471Gly Likely benign ★ same residue
LDLR p.Arg471fs 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
LDLR c.1705+2T>C Likely pathogenic ★★★ same condition
LDLR c.190+4A>T 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-arg471 (accessed [today's date]).

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