LTBP2 p.Pro189=
c.567C>T · rs762037725 · VCV2710450
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0182%, eas)
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 · G>T here scores Δ0.84 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.5 | GERP -3.7 |
| Overall | ||
| CADD | 3.004 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0182%
East Asian · 8/43,892 alleles
Filtering AF
0.00901%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00653%
Overall
0.00119%
19/1,592,442 alleles · ultra-rare
exomes 19/1,440,134 · genomes 0/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0182% | 5,486 |
| Admixed American | 0.0124% | 8,086 |
| South Asian | 0.00114% | 87,804 |
| European (non-Finnish) | 0.000256% | 390,102 |
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
- LTBP2
- Protein
- p.Pro189=
- Coding
- c.567C>T
- MANE Select
- NM_000428
- dbSNP
- rs762037725
- Type
- single nucleotide variant
- Location
- chr14:74586117 (GRCh38)
- Gene constraint
- LOEUF 0.595 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.33
- Residue 189
- the egf-like 1 domain
Similar variants
- LTBP2 p.Pro189Ser Uncertain significance ★★ ⚠ same residue
- LTBP3 p.Gln189Leu Uncertain significance ★ ⚠ same residue
- LTBP2 c.2389-2A>G Likely pathogenic ★★ same type
- LTBP2 c.2659+2T>C Likely pathogenic ★★ same type
- LTBP2 c.2789-1G>A Likely pathogenic ★★ same type
- LTBP2 c.2789-2A>T Likely pathogenic ★★ same type
- LTBP2 c.3652+1G>A Likely pathogenic ★★ same type
- LTBP2 p.Arg299Ter Pathogenic ★★ 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/ltbp2-p-pro189 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown