Is LDLR p.Cys116= (c.348C>T) pathogenic?

LDLR p.Cys116= (c.348C>T) is classified Likely benign in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). Very rare (popmax 8.47e-05%, nfe); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Cys116= (c.348C>T)?

LDLR p.Cys116= (c.348C>T) is associated with familial hypercholesterolemia (ClinVar).

How common is LDLR p.Cys116= (c.348C>T) in the general population?

LDLR p.Cys116= (c.348C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

LDLR p.Cys116=

c.348C>T · rs1205208779 · VCV2773495

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 0.38	GERP -4.3, phastCons 0.025
Overall
CADD	8.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.2e-05% 1/1,613,602 alleles · very rare exomes 1/1,461,296 · genomes 0/152,306 · 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.Cys116=
Coding: c.348C>T
MANE Select: NM_000527
dbSNP: rs1205208779
Type: single nucleotide variant
Location: chr19:11105254 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 116: a disulfide bond; the ldl-receptor class a 3 domain; a UniProt-annotated variant site (in fhcl1; does not affect receptor expression at the cell surface; results in reduced ldl binding; results in reduced ldl uptake and internalization)

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.Cys116Arg Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Cys116Ter Likely pathogenic ★ same residue
LDLR p.Cys116Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Cys116Phe Likely 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.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-cys116 (accessed [today's date]).

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