LTBP4 p.Val686=
c.2058G>A · rs376879859 · VCV1208244
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00212%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.65 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 12.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00212%
European (non-Finnish) · 25/1,177,362 alleles
Filtering AF
0.00146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00162%
26/1,607,876 alleles · very rare
exomes 25/1,455,690 · genomes 1/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00212% | 47,095 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,236 |
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.Val686=
- Coding
- c.2058G>A
- MANE Select
- NM_001042545
- dbSNP
- rs376879859
- Type
- single nucleotide variant
- Location
- chr19:40611863 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.53
- Residue 686
- the egf-like 6; calcium-binding domain
Similar variants
- LTBP4 p.Val686Leu Uncertain significance ★★ ⚠ same residue
- LTBP4 p.Val686Met Uncertain significance ★★ ⚠ same residue
- 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
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-val686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown