Is LDLR p.Asn322= (c.966C>T) pathogenic?

LDLR p.Asn322= (c.966C>T) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-07). Ultra-rare (popmax 0.0253%, sas); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Asn322= (c.966C>T)?

LDLR p.Asn322= (c.966C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Asn322= (c.966C>T) in the general population?

LDLR p.Asn322= (c.966C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

LDLR p.Asn322=

c.966C>T · rs567080879 · VCV630372

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

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 -3.8	GERP -4.9
Overall
CADD	0.621	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,078 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0026% 42/1,613,822 alleles · ultra-rare exomes 38/1,461,546 · genomes 4/152,276 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
Finnishnot grpmax-eligible	0.0047%	21,269
Remaining individualsnot grpmax-eligible	0.0032%	31,251
East Asian	0.00223%	44,874
Admixed American	0.00167%	59,978
European (non-Finnish)	0.00102%	98,330

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.Asn322=
Coding: c.966C>T
MANE Select: NM_000527
dbSNP: rs567080879
Type: single nucleotide variant
Location: chr19:11110677 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 322: the egf-like 1 domain; an α-helix

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.Asn322Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Asn322Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Asn322del Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Asn322fs 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

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-asn322 (accessed [today's date]).

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