LDLR p.Asp354=
c.1062T>C · rs2147241169 · VCV1079082
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
familial hypercholesterolemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.30 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.47 | GERP -3.2, phastCons 0.14 |
| Overall | ||
| CADD | 7.346 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,840 alleles
Overall
6.2e-05%
1/1,613,250 alleles · very rare
exomes 1/1,460,972 · genomes 0/152,278 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- LDLR
- Protein
- p.Asp354=
- Coding
- c.1062T>C
- MANE Select
- NM_000527
- dbSNP
- rs2147241169
- Type
- single nucleotide variant
- Location
- chr19:11111515 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 36 PDB
- Residue 354
- the egf-like 2; calcium-binding domain; a UniProt-annotated variant site (in fhcl1; uncertain significance; munster-2); a UniProt-annotated variant site (in fhcl1; uncertain significance; oklahoma)
Similar variants
- LDLR p.Asp354Asn Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Asp354Gly Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Asp354Val Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Asp354Ala 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.190+4A>T 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-asp354 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown