LTBP2 p.Ala65=
c.195A>C · rs904413497 · VCV1428690
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, afr)
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 -1.8 | GERP -2 |
| Overall | ||
| CADD | 11.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/75,020 alleles
Filtering AF
0.00814%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.000747%
12/1,606,394 alleles · ultra-rare
exomes 5/1,454,074 · genomes 7/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,820 |
| Admixed American | 0.00167% | 59,906 |
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.Ala65=
- Coding
- c.195A>C
- MANE Select
- NM_000428
- dbSNP
- rs904413497
- Type
- single nucleotide variant
- Location
- chr14:74611750 (GRCh38)
- Gene constraint
- LOEUF 0.595 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.33
Similar variants
- LTBP2 p.Ala65Thr Uncertain significance ★ ⚠ same residue
- LTBP3 p.Val65del 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-ala65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown