TPRN p.Ser705=
c.2115C>T · rs372125769 · VCV682509
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0143%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.30 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -2.6 |
| Overall | ||
| CADD | 0.372 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0143%
South Asian · 13/91,086 alleles
Filtering AF
0.00844%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.00607%
98/1,613,436 alleles · ultra-rare
exomes 95/1,461,202 · genomes 3/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0143% | 7,007 |
| European (non-Finnish) | 0.00686% | 14,568 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,618 |
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
- TPRN
- Protein
- p.Ser705=
- Coding
- c.2115C>T
- MANE Select
- NM_001128228
- dbSNP
- rs372125769
- Type
- single nucleotide variant
- Location
- chr9:137192133 (GRCh38)
- Gene constraint
- LOEUF 1.099 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.27 · 1 PDB
- Residue 705
- the 'disordered' region
Similar variants
- TPRN p.Gln414Ter Pathogenic ★★ same type
- TPRN c.1725+5G>A Uncertain significance ★★ same type
- TPRN p.Ala191Val Uncertain significance ★★ ⚠ same type
- TPRN p.Ala302Asp Uncertain significance ★★ ⚠ same type
- TPRN p.Ala390Ser Uncertain significance ★★ ⚠ same type
- TPRN p.Ala695Thr Uncertain significance ★★ ⚠ same type
- TPRN p.Arg231Trp Uncertain significance ★★ ⚠ same type
- TPRN p.Arg284His 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/tprn-p-ser705 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown