Is LDLR p.Tyr679= (c.2037T>C) pathogenic?

LDLR p.Tyr679= (c.2037T>C) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-08). Very rare (popmax 0.00178%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LDLR p.Tyr679= (c.2037T>C)?

LDLR p.Tyr679= (c.2037T>C) is associated with Cardiovascular phenotype, familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Tyr679= (c.2037T>C) in the general population?

LDLR p.Tyr679= (c.2037T>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

LDLR p.Tyr679=

c.2037T>C · rs760436036 · VCV922162

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.63 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP 1.5, phastCons 1
Overall
CADD	6.826	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,040 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,614,176 alleles · very rare exomes 21/1,461,850 · genomes 0/152,326 · joint denominator

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.Tyr679=
Coding: c.2037T>C
MANE Select: NM_000527
dbSNP: rs760436036
Type: single nucleotide variant
Location: chr19:11120419 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 679: the egf-like 3 domain; a β-strand

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.Tyr679Cys Uncertain significance ★ ⚠ same residue
LDLR p.Tyr679fs Pathogenic ★ same residue
LDLR p.Tyr679Ter 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-tyr679 (accessed [today's date]).

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