Is LDLR p.Asp356= (c.1068T>C) pathogenic?

LDLR p.Asp356= (c.1068T>C) is classified Likely benign in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-09). Absent from gnomAD v4.1; Associated with familial hypercholesterolemia.

What condition is associated with LDLR p.Asp356= (c.1068T>C)?

LDLR p.Asp356= (c.1068T>C) is associated with familial hypercholesterolemia (ClinVar).

How common is LDLR p.Asp356= (c.1068T>C) in the general population?

LDLR p.Asp356= (c.1068T>C) is absent from gnomAD v4.1 (gnomAD).

LDLR p.Asp356=

c.1068T>C · rs2515994474 · VCV1973920

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -4.9
Overall
CADD	0.114	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: LDLR
Protein: p.Asp356=
Coding: c.1068T>C
MANE Select: NM_000527
dbSNP: rs2515994474
Type: single nucleotide variant
Location: chr19:11111521 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 356: the egf-like 2; calcium-binding domain; a UniProt-annotated variant site (in fhcl1)

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.Asp356Val Likely pathogenic ★★★ same residue
LDLR p.Asp356Tyr Pathogenic/Likely pathogenic ★★ same residue
LDLR p.Asp356Gly Likely pathogenic ★ same residue
LDLR p.Asp356Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Asp356His Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Asp356Ala Likely 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-asp356 (accessed [today's date]).

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