LTBP2 p.Ser468=
c.1404C>T · rs543286727 · VCV3019470
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0203%, mid)
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 -3.5 | GERP -3.4 |
| Overall | ||
| CADD | 2.476 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0203%
Middle Eastern · 1/4,920 alleles
Filtering AF
0.00826%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00644%
Overall
0.00236%
37/1,568,356 alleles · ultra-rare
exomes 34/1,416,104 · genomes 3/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0203% | 4,920 |
| South Asian | 0.0144% | 6,942 |
| Remaining individualsnot grpmax-eligible | 0.00661% | 15,122 |
| Admixed American | 0.00533% | 18,756 |
| East Asian | 0.00227% | 44,050 |
| African / African-American | 0.00134% | 74,502 |
| European (non-Finnish) | 0.0013% | 77,027 |
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.Ser468=
- Coding
- c.1404C>T
- MANE Select
- NM_000428
- dbSNP
- rs543286727
- Type
- single nucleotide variant
- Location
- chr14:74551346 (GRCh38)
- Gene constraint
- LOEUF 0.595 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.33
Similar variants
- LTBP3 p.Gln468Arg Uncertain significance ★★ ⚠ same residue
- LTBP3 p.Gln468His 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-ser468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown