LTBP4 p.Cys41=
c.123C>T · rs370611661 · VCV1335341
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0828%, nfe)
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 4.5 | GERP 0.95, phastCons 1 |
| Overall | ||
| CADD | 14.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0828%
European (non-Finnish) · 936/1,130,230 alleles
Filtering AF
0.0784%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0766%
Overall
0.0681%
1,019/1,497,404 alleles · ultra-rare
exomes 935/1,345,366 · genomes 84/152,038 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0828% | 1,208 |
| Remaining individualsnot grpmax-eligible | 0.055% | 1,818 |
| Admixed American | 0.0493% | 2,030 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0402% | 2,488 |
| African / African-American | 0.0175% | 5,730 |
| Finnishnot grpmax-eligible | 0.00902% | 11,081 |
| South Asian | 0.00125% | 79,934 |
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.Cys41=
- Coding
- c.123C>T
- MANE Select
- NM_001042545
- dbSNP
- rs370611661
- Type
- single nucleotide variant
- Location
- chr19:40601510 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.53
Similar variants
- 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
- LTBP4 p.Ala1090Thr Uncertain significance ★★ ⚠ same type
- LTBP4 p.Ala1125Thr 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-cys41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown