TPP1 p.Pro469=
c.1407A>G · rs750546113 · VCV1225378
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.025%, amr)
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 -2.9 | GERP -2.1 |
| Overall | ||
| CADD | 7.713 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.025%
Admixed American · 15/60,024 alleles
Filtering AF
0.0153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0124%
Overall
0.00161%
26/1,614,126 alleles · ultra-rare
exomes 19/1,461,892 · genomes 7/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.025% | 4,002 |
| African / African-American | 0.00267% | 37,499 |
| East Asian | 0.00223% | 44,888 |
| European (non-Finnish) | 0.000678% | 147,502 |
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
- TPP1
- Protein
- p.Pro469=
- Coding
- c.1407A>G
- MANE Select
- NM_000391
- dbSNP
- rs750546113
- Type
- single nucleotide variant
- Location
- chr11:6615189 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.70 · 2 PDB
- Residue 469
- a β-strand; the peptidase s53 domain
Similar variants
- TPP1 c.1075+2T>C Pathogenic/Likely pathogenic ★★ same type
- TPP1 c.1076-2A>G Pathogenic/Likely pathogenic ★★ same type
- TPP1 c.1076-2A>T Pathogenic ★★ same type
- TPP1 c.1146-1G>A Likely pathogenic ★★ same type
- TPP1 c.1425+1G>A Likely pathogenic ★★ same type
- TPP1 c.1551+1G>A Pathogenic/Likely pathogenic ★★ same type
- TPP1 c.1551+1G>C Pathogenic/Likely pathogenic ★★ same type
- TPP1 c.1551+1G>T Pathogenic/Likely 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/tpp1-p-pro469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown