TPSB2 p.Pro103Leu
c.308C>T · VCV4598394
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0041%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.251 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -0.69 | GERP -3.1 |
| Regional constraint | o/e 0.37 | unconstrained · MANE · 123 bp · p 5.7e-05 · regional, not allelic |
| Overall | ||
| CADD | 13.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0041%
African / African-American · 1/24,406 alleles
Filtering AF
0.000235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00017%
Overall
0.00082%
7/853,968 alleles · very rare
exomes 7/799,310 · genomes 0/54,658 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0041% | 24,406 |
| South Asian | 0.00189% | 52,772 |
| European (non-Finnish) | 0.000801% | 124,902 |
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
- TPSB2
- Protein
- p.Pro103Leu
- Coding
- c.308C>T
- MANE Select
- NM_024164
- Type
- single nucleotide variant
- Location
- chr16:1229382 (GRCh38)
- Gene constraint
- LOEUF 1.803 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.79 · 13 PDB
- Residue 103
- the peptidase s1 domain; a β-strand
Similar variants
- TPSB2 p.Pro103Arg Uncertain significance ★ same residue
- TPSB2 p.Gly23Val Benign ★★ same type
- TPSB2 p.Val76Leu Benign ★★ same type
- TPSB2 p.Ala120Val Uncertain significance ★ same type
- TPSB2 p.Ala123Thr Uncertain significance ★ same type
- TPSB2 p.Ala16Ser Uncertain significance ★ same type
- TPSB2 p.Ala21Val Uncertain significance ★ same type
- TPSB2 p.Ala25Thr 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/tpsb2-p-pro103leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown