LDLR p.Thr635=
c.1905A>G · rs146559461 · VCV3070360
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Conditions
1
hypercholesterolemia, familial, 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.30 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8 | GERP -4.4 |
| Overall | ||
| CADD | 0.144 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,052 alleles
Overall
0.000124%
2/1,614,024 alleles · very rare
exomes 1/1,461,728 · genomes 1/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 75,052 |
| European (non-Finnish) | 8.48e-05% | 1,179,884 |
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.Thr635=
- Coding
- c.1905A>G
- MANE Select
- NM_000527
- dbSNP
- rs146559461
- Type
- single nucleotide variant
- Location
- chr19:11120151 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.81 · 36 PDB
- Residue 635
- a turn
Similar variants
- LDLR p.Thr635Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- LDLR p.Thr635fs Pathogenic/Likely pathogenic ★★ same residue
- LDLR p.Thr635Pro Uncertain significance ★ ⚠ 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
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-thr635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown