TPP1 p.Ser334=
c.1002C>T · rs796053432 · VCV207554
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0011%, 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 -3.9 | GERP -2.6 |
| Overall | ||
| CADD | 0.746 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,080 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.00062%
10/1,613,890 alleles · very rare
exomes 9/1,461,688 · genomes 1/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000763% | 131,114 |
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.Ser334=
- Coding
- c.1002C>T
- MANE Select
- NM_000391
- dbSNP
- rs796053432
- Type
- single nucleotide variant
- Location
- chr11:6616388 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.70 · 2 PDB
- Residue 334
- an α-helix; 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-ser334 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown