TPSAB1 p.Pro111=
c.333A>C · VCV4927116
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.129%, sas)
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 -13 | GERP -3.4 |
| Overall | ||
| CADD | 2.963 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
South Asian · 101/78,362 alleles
Filtering AF
0.108%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.101%
Overall
0.00964%
139/1,442,016 alleles · rare
exomes 129/1,310,620 · genomes 10/131,396 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.129% | 776 |
| Remaining individualsnot grpmax-eligible | 0.00885% | 11,303 |
| East Asian | 0.00519% | 19,276 |
| Finnishnot grpmax-eligible | 0.00365% | 27,373 |
| European (non-Finnish) | 0.00253% | 39,527 |
| Admixed American | 0.00209% | 47,946 |
| African / African-American | 0.00149% | 67,036 |
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
- TPSAB1
- Protein
- p.Pro111=
- Coding
- c.333A>C
- MANE Select
- NM_003294
- Type
- single nucleotide variant
- Location
- chr16:1241533 (GRCh38)
- Gene constraint
- LOEUF 1.9 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 91.80 · 22 PDB
- Residue 111
- the peptidase s1 domain
Similar variants
- TPSAB1 p.Val76Met Uncertain significance ★★ same type
- TPSAB1 c.1-105C>A Benign ★★ same type
- TPSAB1 c.233+12G>A Benign ★★ same type
- TPSAB1 c.233+30G>C Benign ★★ same type
- TPSAB1 c.61+75T>C Benign ★★ same type
- TPSAB1 c.62-27C>T Benign ★★ same type
- TPSAB1 c.62-40C>G Benign ★★ same type
- TPSAB1 c.663+12C>G Benign ★★ 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/tpsab1-p-pro111 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown