TPP1 p.Phe176=
c.528T>C · rs2493799557 · VCV2034346
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 0.44 | GERP -2, phastCons 0.81 |
| Overall | ||
| CADD | 1.437 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TPP1
- Protein
- p.Phe176=
- Coding
- c.528T>C
- MANE Select
- NM_000391
- dbSNP
- rs2493799557
- Type
- single nucleotide variant
- Location
- chr11:6617134 (GRCh38)
- Gene constraint
- LOEUF 0.78 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.70 · 2 PDB
- Residue 176
- an α-helix
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-phe176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown