TPP1 p.Pro202=
c.606C>T · rs768687217 · VCV1146816
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 -1 | GERP -2.5 |
| Overall | ||
| CADD | 4.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,086 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00136%
22/1,614,024 alleles · very rare
exomes 21/1,461,860 · genomes 1/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,181 |
| Admixed American | 0.00333% | 30,001 |
| European (non-Finnish) | 0.00119% | 84,287 |
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.Pro202=
- Coding
- c.606C>T
- MANE Select
- NM_000391
- dbSNP
- rs768687217
- Type
- single nucleotide variant
- Location
- chr11:6617056 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.70 · 2 PDB
- Residue 202
- a UniProt-annotated variant site (in cln2; displays no residual enzyme activity; altered intracellular trafficking); the peptidase s53 domain; an α-helix
Similar variants
- TPP1 p.Pro202Leu Pathogenic/Likely pathogenic ★★ same residue
- TPP1 p.Pro202His Likely pathogenic ★ same residue
- 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
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-pro202 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown