LTBP2 p.Pro1626=
c.4878G>A · rs371023355 · VCV1921435
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.73 | GERP -3.5 |
| Overall | ||
| CADD | 6.789 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,032 alleles
Filtering AF
0.00153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0013%
Overall
0.00192%
31/1,614,022 alleles · very rare
exomes 27/1,461,646 · genomes 4/152,376 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,016 |
| European (non-Finnish) | 0.0022% | 45,386 |
| South Asian | 0.0022% | 45,541 |
| Finnishnot grpmax-eligible | 0.00157% | 63,822 |
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.Pro1626=
- Coding
- c.4878G>A
- MANE Select
- NM_000428
- dbSNP
- rs371023355
- Type
- single nucleotide variant
- Location
- chr14:74503229 (GRCh38)
- Gene constraint
- LOEUF 0.595 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.33
- Residue 1626
- the tb 4 domain
Similar variants
- LTBP2 p.Pro1626Leu 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
- LTBP2 p.Cys1438Tyr 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-pro1626 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown