Is LDLR p.Ser786= (c.2358C>T) pathogenic?

LDLR p.Ser786= (c.2358C>T) is classified Conflicting classifications of pathogenicity in LDLR (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-31). Rare (popmax 0.194%, eas); Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Ser786= (c.2358C>T)?

LDLR p.Ser786= (c.2358C>T) is associated with hypercholesterolemia, familial, 1, familial hypercholesterolemia (ClinVar).

How common is LDLR p.Ser786= (c.2358C>T) in the general population?

LDLR p.Ser786= (c.2358C>T) is rare (popmax 0.194%, eas) (gnomAD).

LDLR p.Ser786=

c.2358C>T · rs183255090 · VCV491665

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.194%, eas)

Conditions

hypercholesterolemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP -5.2	GERP -2.8
Overall
CADD	1.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.194% East Asian · 87/44,874 alleles

Filtering AF 0.161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.00991% 160/1,614,108 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.194%	516
South Asian	0.0549%	1,822
Remaining individualsnot grpmax-eligible	0.0288%	3,473
African / African-American	0.00267%	37,516
European (non-Finnish)	0.000254%	393,334

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.Ser786=
Coding: c.2358C>T
MANE Select: NM_000527
dbSNP: rs183255090
Type: single nucleotide variant
Location: chr19:11128054 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB

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

Disease context

hypercholesterolemia, familial, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial hypercholesterolemia

Similar variants

LDLR p.Ser786Cys Conflicting classifications of pathogenicity ★ ⚠ 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
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-ser786 (accessed [today's date]).

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