TCAP p.Arg166Ser
c.498A>T · VCV4935038
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8801 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8801 | likely pathogenic · top 1% in TCAP |
|---|---|---|
| REVEL | 0.648 | pathogenic-leaning |
| SaProt | LLR -6.35 | 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 1.4 | GERP -2.4, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 746 bp · p 0.44 · regional, not allelic |
| Overall | ||
| CADD | 23.1 | 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.Arg166Ser
- Coding
- c.498A>T
- MANE Select
- NM_003673
- Type
- single nucleotide variant
- Location
- chr17:39666103 (GRCh38)
- Gene constraint
- LOEUF 1.374 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.89 · 2 PDB
- Residue 166
- the 'disordered' region
Similar variants
- TCAP p.Arg166Lys Uncertain significance ★★ same residue
- TCAP p.Arg166Gly Uncertain significance ★ ⚠ same residue
- TCAP c.110+5G>T Likely pathogenic ★★ same type
- TCAP p.Cys57Ter Pathogenic/Likely pathogenic ★★ same type
- TCAP p.Gln53Ter Pathogenic/Likely pathogenic ★★ same type
- TCAP p.Glu35Ter Pathogenic ★★ same type
- TCAP p.Trp22Ter Pathogenic/Likely pathogenic ★★ same type
- TCAP p.Trp25Ter 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/tcap-p-arg166ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown