Is LDLR p.Asp342= (c.1026C>T) pathogenic?

LDLR p.Asp342= (c.1026C>T) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-10-15). Very rare (popmax 0.00668%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Asp342= (c.1026C>T)?

LDLR p.Asp342= (c.1026C>T) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Asp342= (c.1026C>T) in the general population?

LDLR p.Asp342= (c.1026C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

LDLR p.Asp342=

c.1026C>T · rs780563386 · VCV701123

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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 -2.8	GERP -4.9
Overall
CADD	6.622	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,894 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000806% 13/1,613,680 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,965
Admixed American	0.00667%	14,995
Remaining individualsnot grpmax-eligible	0.0032%	31,238
African / African-American	0.00133%	74,946
European (non-Finnish)	0.000254%	393,329

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.Asp342=
Coding: c.1026C>T
MANE Select: NM_000527
dbSNP: rs780563386
Type: single nucleotide variant
Location: chr19:11110737 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 342: the egf-like 1 domain; a UniProt-annotated variant site (in fhcl1; uncertain significance; new york-1); a UniProt-annotated variant site (in fhcl1; benign); a β-strand; a disulfide bond

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.Asp342Tyr Uncertain significance ★★★ ⚠ same residue
LDLR p.Asp342Asn Benign ★★★ same residue
LDLR p.Asp342His Uncertain significance ★★ ⚠ same residue
LDLR p.Asp342Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Asp342fs 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

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-asp342 (accessed [today's date]).

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