LTBP2 p.Pro765=
c.2295C>T · rs148839448 · VCV1534934
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
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 -4 | GERP -3.4 |
| Overall | ||
| CADD | 0.746 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,062 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00564%
91/1,613,134 alleles · ultra-rare
exomes 82/1,460,768 · genomes 9/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,059 |
| Admixed American | 0.0133% | 7,504 |
| African / African-American | 0.0107% | 9,381 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,819 |
| European (non-Finnish) | 0.00458% | 21,853 |
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.Pro765=
- Coding
- c.2295C>T
- MANE Select
- NM_000428
- dbSNP
- rs148839448
- Type
- single nucleotide variant
- Location
- chr14:74528556 (GRCh38)
- Gene constraint
- LOEUF 0.595 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.33
- Residue 765
- the 'disordered' region
Similar variants
- 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
- LTBP2 p.Cys1438Tyr Likely pathogenic ★★ same type
- LTBP2 p.Gln1533Ter Pathogenic/Likely 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-pro765 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown