Is LDLR p.Arg744= (c.2232A>G) pathogenic?

LDLR p.Arg744= (c.2232A>G) is classified Benign in LDLR (ClinVar, Multiple submitters, 22 submitters; last evaluated 2026-02-04). Common (popmax 94.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Arg744= (c.2232A>G)?

LDLR p.Arg744= (c.2232A>G) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

LDLR p.Arg744=

Q: How common is LDLR p.Arg744= (c.2232A>G) in the general population?

LDLR p.Arg744= (c.2232A>G) is common (popmax 94.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2232A>G · rs5927 · VCV252262

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 22 submitters

gnomAD v4.1

Common

common (popmax 94.8%, eas) — 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 -0.029	GERP -3.3
Overall
CADD	1.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.8% East Asian · 42,543/44,864 alleles

Filtering AF 94.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 93.8%

Overall 76% 1,226,293/1,613,474 alleles · common exomes 1,112,203/1,461,492 · genomes 114,090/151,982 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	94.8%	1
Admixed American	86.5%	1
Finnishnot grpmax-eligible	76.7%	1
Remaining individualsnot grpmax-eligible	75.8%	1
South Asian	75.5%	1
European (non-Finnish)	75.3%	1
Ashkenazi Jewishnot grpmax-eligible	73%	1
Middle Eastern	72.5%	1
African / African-American	68.6%	1
Amishnot grpmax-eligible	67.6%	1

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.Arg744=
Coding: c.2232A>G
MANE Select: NM_000527
dbSNP: rs5927
Type: single nucleotide variant
Location: chr19:11123265 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 744: the 'clustered o-linked oligosaccharides' region; the 'disordered' region

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.Arg744Ter Pathogenic ★★ same residue
LDLR p.Arg744Gln Uncertain significance ★★★ same residue
LDLR p.Arg744fs Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Arg744Trp Uncertain significance ★★ same residue
LDLR p.Arg744_Pro745dup 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

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-arg744 (accessed [today's date]).

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