LTBP4 p.Pro533=
c.1599C>T · rs767751664 · VCV508032
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000933%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.3 | GERP -4.3 |
| Overall | ||
| CADD | 11.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000933%
European (non-Finnish) · 11/1,178,858 alleles
Filtering AF
0.000501%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000683%
11/1,611,484 alleles · very rare
exomes 10/1,459,302 · genomes 1/152,182 · 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
- LTBP4
- Protein
- p.Pro533=
- Coding
- c.1599C>T
- MANE Select
- NM_001042545
- dbSNP
- rs767751664
- Type
- single nucleotide variant
- Location
- chr19:40609786 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.53
- Residue 533
- the 'disordered' region
Similar variants
- LTBP4 c.1307-2A>G Pathogenic/Likely pathogenic ★★ same type
- LTBP4 p.Arg677Ter Pathogenic/Likely pathogenic ★★ same type
- LTBP4 p.Arg691Ter Pathogenic ★★ same type
- LTBP4 c.2944+5G>C Uncertain significance ★★ same type
- LTBP4 c.3070+4C>T Uncertain significance ★★ same type
- LTBP4 c.*121C>G Uncertain significance ★★ same type
- LTBP4 p.Ala1090Thr Uncertain significance ★★ ⚠ same type
- LTBP4 p.Ala1125Thr Uncertain significance ★★ ⚠ same type
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/ltbp4-p-pro533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown