TCAP p.Trp25Arg
c.73T>C · VCV3454008
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9783 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9783 | likely pathogenic · top 1% in TCAP |
|---|---|---|
| REVEL | 0.661 | pathogenic-leaning |
| SaProt | LLR -6.21 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic |
| Overall | ||
| CADD | 25.4 | 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
- TCAP
- Protein
- p.Trp25Arg
- Coding
- c.73T>C
- MANE Select
- NM_003673
- Type
- single nucleotide variant
- Location
- chr17:39665432 (GRCh38)
- Gene constraint
- LOEUF 1.374 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.89 · 2 PDB
- Residue 25
- a β-strand
Similar variants
- TCAP p.Trp25Ter Pathogenic/Likely pathogenic ★★ same residue
- TCAP p.Gln53Ter Pathogenic/Likely pathogenic ★★ same condition
- TCAP c.110+4A>G Uncertain significance ★★ same condition
- TCAP p.Arg130His Uncertain significance ★★ ⚠ same condition
- TCAP p.Arg153Ser Uncertain significance ★★ ⚠ same condition
- TCAP p.Arg154Cys Uncertain significance ★★ ⚠ same condition
- TCAP p.Arg154Ser Uncertain significance ★★ same condition
- TCAP p.Arg158Gly Uncertain significance ★★ ⚠ same condition
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/tcap-p-trp25arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown