LDLR p.Cys698Ter
c.2094C>A · rs879255137 · VCV2848117
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
familial hypercholesterolemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 14 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.55 | GERP -3.8, phastCons 0.027 |
| Overall | ||
| CADD | 35.0 | 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
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.Cys698Ter
- Coding
- c.2094C>A
- MANE Select
- NM_000527
- dbSNP
- rs879255137
- Type
- single nucleotide variant
- Location
- chr19:11120476 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 36 PDB
- Residue 698
- the egf-like 3 domain; a disulfide bond
Similar variants
- LDLR p.Cys698Arg Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Cys698Phe Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Cys698Ser Likely pathogenic ★★ same residue
- LDLR p.Cys698Tyr Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Cys698fs Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Cys698Gly Uncertain significance ★ ⚠ same residue
- LDLR p.Cys698Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
- LDLR c.1186+5G>A Likely 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-cys698ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown