TPR p.Ser849Pro
c.2545T>C · VCV4598363
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.7023 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.7023 | likely pathogenic |
|---|---|---|
| REVEL | 0.178 | moderately benign-leaning |
| SaProt | LLR -11.80 | damaging |
| ⇒ AlphaMissense and SaProt call this damaging; REVEL does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.44 | GERP -2.8, phastCons 0.77 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 16 kb · p 0.00045 · regional, not allelic |
| Overall | ||
| CADD | 19.77 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- TPR
- Protein
- p.Ser849Pro
- Coding
- c.2545T>C
- MANE Select
- NM_003292
- Type
- single nucleotide variant
- Location
- chr1:186351395 (GRCh38)
- Gene constraint
- LOEUF 0.203 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 61.60 · 4 PDB
Similar variants
- TPR p.Thr1751Ala Uncertain significance ★★ ⚠ same type
- TPR p.Arg1832His Likely benign ★★ same type
- TPR p.Arg467= Benign/Likely benign ★★ same type
- TPR p.Leu1314= Benign ★★ same type
- TPR p.Pro2168Ser Benign ★★ same type
- TPR p.Thr762= Benign ★★ same type
- TPR c.2610+5G>A Uncertain significance ★ same type
- TPR p.Ala1025Thr 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/tpr-p-ser849pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown