Is LDLRAP1 p.Ser288= (c.864G>C) pathogenic?

LDLRAP1 p.Ser288= (c.864G>C) is classified Likely benign in LDLRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). Absent from gnomAD v4.1; Associated with hypercholesterolemia, familial, 4.

What condition is associated with LDLRAP1 p.Ser288= (c.864G>C)?

LDLRAP1 p.Ser288= (c.864G>C) is associated with hypercholesterolemia, familial, 4 (ClinVar).

How common is LDLRAP1 p.Ser288= (c.864G>C) in the general population?

LDLRAP1 p.Ser288= (c.864G>C) is absent from gnomAD v4.1 (gnomAD).

LDLRAP1 p.Ser288=

c.864G>C · rs761310334 · VCV2895950

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hypercholesterolemia, familial, 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.3	GERP -3.7
Overall
CADD	1.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LDLRAP1
Protein: p.Ser288=
Coding: c.864G>C
MANE Select: NM_015627
dbSNP: rs761310334
Type: single nucleotide variant
Location: chr1:25566929 (GRCh38)
Gene constraint: LOEUF 1.083 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.90 · 1 PDB

Full LDLRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypercholesterolemia, familial, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LDLRAP1 p.Ser288Leu Uncertain significance ★ ⚠ same residue
LDLRAP1 c.344+1G>A Pathogenic/Likely pathogenic ★★ same condition
LDLRAP1 c.460-1G>A Pathogenic/Likely pathogenic ★★ same condition
LDLRAP1 c.532+1G>A Likely pathogenic ★★ same condition
LDLRAP1 c.533-1G>A Likely pathogenic ★★ same condition
LDLRAP1 c.617-2A>G Likely pathogenic ★★ same condition
LDLRAP1 c.89-1G>C Pathogenic ★★ same condition
LDLRAP1 p.Gln136Ter 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/ldlrap1-p-ser288 (accessed [today's date]).

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