TPPP p.Pro19=
c.57G>A · rs138862056 · VCV730677
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.923%, afr)
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 -6.9 | GERP -2.8 |
| Overall | ||
| CADD | 5.515 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.923%
African / African-American · 690/74,770 alleles
Filtering AF
0.866%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.843%
Overall
0.0547%
878/1,604,730 alleles · rare
exomes 460/1,452,384 · genomes 418/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.923% | 108 |
| Admixed American | 0.0765% | 1,308 |
| Remaining individualsnot grpmax-eligible | 0.0516% | 1,939 |
| Middle Eastern | 0.0168% | 5,946 |
| European (non-Finnish) | 0.00901% | 11,096 |
| South Asian | 0.00445% | 22,478 |
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
- TPPP
- Protein
- p.Pro19=
- Coding
- c.57G>A
- MANE Select
- NM_007030
- dbSNP
- rs138862056
- Type
- single nucleotide variant
- Location
- chr5:678004 (GRCh38)
- Gene constraint
- LOEUF 0.755 · pLI 0.44 (gnomAD)
- Structure
- AlphaFold pLDDT 79.16 · 3 PDB
- Residue 19
- the 'mediates interaction with limk1' region; the 'disordered' region
Similar variants
- TPPP p.Arg57= Benign ★★ same type
- TPPP p.Gly39Ala Benign ★★ same type
- TPPP p.Ala38Val Uncertain significance ★ ⚠ same type
- TPPP p.Ala54Thr Uncertain significance ★ ⚠ same type
- TPPP p.Ala8Ser Uncertain significance ★ ⚠ same type
- TPPP p.Arg26Gln Uncertain significance ★ ⚠ same type
- TPPP p.Gly39Ser Uncertain significance ★ ⚠ same type
- TPPP p.Gly73Ser 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/tppp-p-pro19 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown