Is LDLR p.Cys173= (c.519C>T) pathogenic?

LDLR p.Cys173= (c.519C>T) is classified Likely benign in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-31). Very rare (popmax 0.0011%, sas); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Cys173= (c.519C>T)?

LDLR p.Cys173= (c.519C>T) is associated with familial hypercholesterolemia (ClinVar).

How common is LDLR p.Cys173= (c.519C>T) in the general population?

LDLR p.Cys173= (c.519C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

LDLR p.Cys173=

c.519C>T · rs769318035 · VCV1086089

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -2.6	GERP -5.1
Overall
CADD	7.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,080 alleles · very rare exomes 4/1,461,740 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,086
European (non-Finnish)	0.000254%	393,340

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.Cys173=
Coding: c.519C>T
MANE Select: NM_000527
dbSNP: rs769318035
Type: single nucleotide variant
Location: chr19:11105425 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 173: a UniProt-annotated variant site (in fhcl1; greece-1); a UniProt-annotated variant site (in fhcl1); the 'binding to getah virus e1-e2 spike glycoproteins' region; a β-strand; a disulfide bond; the ldl-receptor class a 4 domain

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.Cys173Arg Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Cys173Trp Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Cys173Tyr Likely pathogenic ★★ same residue
LDLR p.Cys173Gly Likely pathogenic ★★ same residue
LDLR p.Cys173Ter Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Cys173Ser Pathogenic same residue
LDLR c.1186+5G>A Likely pathogenic ★★★ same condition
LDLR c.1359-1G>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-cys173 (accessed [today's date]).

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