Is LDLR p.Cys839= (c.2517C>T) pathogenic?

LDLR p.Cys839= (c.2517C>T) is classified Likely benign in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). Absent from gnomAD v4.1; Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Cys839= (c.2517C>T)?

LDLR p.Cys839= (c.2517C>T) is associated with familial hypercholesterolemia (ClinVar).

How common is LDLR p.Cys839= (c.2517C>T) in the general population?

LDLR p.Cys839= (c.2517C>T) is absent from gnomAD v4.1 (gnomAD).

LDLR p.Cys839=

c.2517C>T · rs2512461715 · VCV2749214

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial hypercholesterolemia

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 0.72	GERP 1.4, phastCons 0.26
Overall
CADD	7.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LDLR
Protein: p.Cys839=
Coding: c.2517C>T
MANE Select: NM_000527
dbSNP: rs2512461715
Type: single nucleotide variant
Location: chr19:11129640 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 839: the 'required for mylip-triggered down-regulation of ldlr' region

Full LDLR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial hypercholesterolemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDLR p.Cys839Tyr Uncertain significance ★ ⚠ 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.190+4A>T Likely pathogenic ★★★ same condition
LDLR c.2140+1G>A Pathogenic ★★★ same condition
LDLR c.2389+2T>G Pathogenic ★★★ same condition
LDLR c.313+1G>A 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-cys839 (accessed [today's date]).

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