TPP2 c.784+105C>T
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 29.3%, nfe) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +105 | deep intronic (+105 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.22 | GERP -1.1 |
| Non-coding constraint | Z 1.08 | 1 kb window · o/e 0.92 · regional · uncalibrated |
| Overall | ||
| CADD | 4.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
29.3%
European (non-Finnish) · 265,896/906,578 alleles
Filtering AF
29.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 29.2%
Overall
26.5%
330,356/1,244,970 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 29.3% | 3 |
| Finnishnot grpmax-eligible | 28.9% | 3 |
| Middle Eastern | 25.2% | 4 |
| Remaining individualsnot grpmax-eligible | 25.1% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 22.1% | 5 |
| African / African-American | 21% | 5 |
| South Asian | 18.3% | 5 |
| Amishnot grpmax-eligible | 16.7% | 6 |
| Admixed American | 14.4% | 7 |
| East Asian | 0.0825% | 1,212 |
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
- TPP2
- Coding
- c.784+105C>T
- MANE Select
- NM_001330588
- dbSNP
- rs17507043
- Type
- single nucleotide variant
- Location
- chr13:102623145 (GRCh38)
- Gene constraint
- LOEUF 0.29 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 91.98
Similar variants
- TPP2 p.Ala1143Ser Uncertain significance ★★ ⚠ same type
- TPP2 p.Ala460Thr Uncertain significance ★★ ⚠ same type
- TPP2 p.Ala619Thr Uncertain significance ★★ ⚠ same type
- TPP2 p.Ala648Asp Uncertain significance ★★ ⚠ same type
- TPP2 p.Arg1072Gln Uncertain significance ★★ ⚠ same type
- TPP2 p.Arg598His Uncertain significance ★★ ⚠ same type
- TPP2 p.Arg893Cys Uncertain significance ★★ ⚠ same type
- TPP2 p.Arg902His 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/tpp2-c-784-plus-105c-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown