Is LDLR p.Ser306Ter (c.917C>A) pathogenic?

LDLR p.Ser306Ter (c.917C>A) is classified Pathogenic in LDLR (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-25). No allele count reported in gnomAD v4.1 (AN 1,608,984); Associated with hypercholesterolemia, familial, 1.

What condition is associated with LDLR p.Ser306Ter (c.917C>A)?

LDLR p.Ser306Ter (c.917C>A) is associated with hypercholesterolemia, familial, 1 (ClinVar).

How common is LDLR p.Ser306Ter (c.917C>A) in the general population?

LDLR p.Ser306Ter (c.917C>A) is no allele count reported in gnomAD v4.1 (AN 1,608,984) (gnomAD).

LDLR p.Ser306Ter

c.917C>A · rs11547917 · VCV251523

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,984)

Conditions

hypercholesterolemia, familial, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 18
Splicing
SpliceAI	Δ0.96	donor gain · deltas
Pangolin	Δ0.69	gain · loss 0.28 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP -2.2, phastCons 1
Overall
CADD	47.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,608,984). 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.Ser306Ter
Coding: c.917C>A
MANE Select: NM_000527
dbSNP: rs11547917
Type: single nucleotide variant
Location: chr19:11107491 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.81 · 36 PDB
Residue 306: the ldl-receptor class a 7 domain; a UniProt-annotated variant site (in fhcl1; uncertain significance; amsterdam); a β-strand

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.Ser306Leu Pathogenic/Likely pathogenic ★★ 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-ser306ter (accessed [today's date]).

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