Is LDLR p.Thr62= (c.186G>A) pathogenic?

LDLR p.Thr62= (c.186G>A) is classified Conflicting classifications of pathogenicity in LDLR (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-03-06). Rare (popmax 0.148%, mid); Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Thr62= (c.186G>A)?

LDLR p.Thr62= (c.186G>A) is associated with familial hypercholesterolemia, hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Thr62= (c.186G>A) in the general population?

LDLR p.Thr62= (c.186G>A) is rare (popmax 0.148%, mid) (gnomAD).

LDLR p.Thr62=

c.186G>A · rs55958434 · VCV700381

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

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 -13	GERP -4.4
Overall
CADD	0.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00445% 65/1,461,178 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
East Asian	0.0156%	6,410
Admixed American	0.00833%	12,000
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.00339%	29,496
South Asian	0.0011%	91,062

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.Thr62=
Coding: c.186G>A
MANE Select: NM_000527
dbSNP: rs55958434
Type: single nucleotide variant
Location: chr19:11100341 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 62: a turn; a disulfide bond; the ldl-receptor class a 1 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

Also linked: hypercholesterolemia, familial, 1

Similar variants

LDLR p.Thr62Arg Uncertain significance ★★★ ⚠ same residue
LDLR p.Thr62Met 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.1705+2T>C Likely pathogenic ★★★ same condition
LDLR c.190+4A>T Likely pathogenic ★★★ same condition
LDLR c.2140+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-thr62 (accessed [today's date]).

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