Is LDLR p.Ser849fs (c.2544dup) pathogenic?

LDLR p.Ser849fs (c.2544dup) is classified Pathogenic/Likely pathogenic in LDLR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-25). No gnomAD frequency available for this variant; Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Ser849fs (c.2544dup)?

LDLR p.Ser849fs (c.2544dup) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Ser849fs (c.2544dup) in the general population?

LDLR p.Ser849fs (c.2544dup) is no gnomAD frequency available for this variant (gnomAD).

LDLR p.Ser849fs

c.2544dup · rs879255222 · VCV252349

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hypercholesterolemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (17 of 18, 7 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LDLR
Protein: p.Ser849fs
Coding: c.2544dup
MANE Select: NM_000527
dbSNP: rs879255222
Type: Duplication
Location: chr19:11129663 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 849: the 'required for mylip-triggered down-regulation of ldlr' region

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

Similar variants

LDLR p.Ser849Ter Likely pathogenic ★★★ same residue
LDLR p.Ser849Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
LDLR p.Glu763fs Likely pathogenic ★★★ same condition
LDLR p.Cys803_Leu808dup Uncertain significance ★★★ same condition
LDLR c.313+1dup Pathogenic/Likely pathogenic ★★ same condition
LDLR c.313+2dup Pathogenic/Likely pathogenic ★★ same condition
LDLR c.314-446_1187-386dup Pathogenic/Likely pathogenic ★★ same condition
LDLR p.Ala13fs 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-ser849fs (accessed [today's date]).

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