Is LDLR p.Pro171= (c.513C>T) pathogenic?

LDLR p.Pro171= (c.513C>T) is classified Likely benign in LDLR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). Very rare (popmax 0.00333%, amr); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Pro171= (c.513C>T)?

LDLR p.Pro171= (c.513C>T) is associated with familial hypercholesterolemia (ClinVar).

How common is LDLR p.Pro171= (c.513C>T) in the general population?

LDLR p.Pro171= (c.513C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

LDLR p.Pro171=

c.513C>T · rs747327435 · VCV1108751

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -20	GERP -5.1
Overall
CADD	0.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000496% 8/1,613,946 alleles · very rare exomes 7/1,461,726 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,940
European (non-Finnish)	0.000339%	295,005

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.Pro171=
Coding: c.513C>T
MANE Select: NM_000527
dbSNP: rs747327435
Type: single nucleotide variant
Location: chr19:11105419 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 171: the 'binding to getah virus e1-e2 spike glycoproteins' region; 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.Pro171Thr Uncertain significance ★ ⚠ same residue
LDLR p.Pro171Leu 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

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-pro171 (accessed [today's date]).

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