TSEN34 p.Ser166=
c.498T>G · rs201833183 · VCV2650427
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00195%, nfe)
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 -0.14 | GERP -0.8 |
| Overall | ||
| CADD | 8.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00195%
European (non-Finnish) · 23/1,180,036 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00149%
24/1,614,232 alleles · very rare
exomes 22/1,461,894 · genomes 2/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00195% | 51,306 |
| African / African-American | 0.00133% | 75,068 |
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
- TSEN34
- Protein
- p.Ser166=
- Coding
- c.498T>G
- MANE Select
- NM_001077446
- dbSNP
- rs201833183
- Type
- single nucleotide variant
- Location
- chr19:54192126 (GRCh38)
- Gene constraint
- LOEUF 1.159 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.74 · 6 PDB
- Residue 166
- the 'disordered' region
Similar variants
- TSEN34 p.Arg253His Uncertain significance ★★ ⚠ same type
- TSEN34 p.Arg25Cys Uncertain significance ★★ ⚠ same type
- TSEN34 p.Arg88Cys Uncertain significance ★★ ⚠ same type
- TSEN34 p.Asp148Tyr Uncertain significance ★★ ⚠ same type
- TSEN34 p.Gly39Arg Uncertain significance ★★ ⚠ same type
- TSEN34 p.Ile116Phe Uncertain significance ★★ ⚠ same type
- TSEN34 p.Leu227Val Uncertain significance ★★ ⚠ same type
- TSEN34 p.Leu2Pro 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/tsen34-p-ser166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown