PAX8 p.Pro25=
c.75T>C · rs1321193232 · VCV743765
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -0.22 | GERP -3.7, phastCons 0.016 |
| Overall | ||
| CADD | 1.606 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,030 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000186%
3/1,614,194 alleles · very rare
exomes 3/1,461,820 · genomes 0/152,374 · joint denominator
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
- PAX8
- Protein
- p.Pro25=
- Coding
- c.75T>C
- MANE Select
- NM_003466
- dbSNP
- rs1321193232
- Type
- single nucleotide variant
- Location
- chr2:113246870 (GRCh38)
- Gene constraint
- LOEUF 0.415 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.09 · 1 PDB
- Residue 25
- a DNA-binding region; the 'pai subdomain' region
Similar variants
- PAX8 p.Arg133Gln Pathogenic/Likely pathogenic ★★ same type
- PAX8 c.*1765G>A Uncertain significance ★★ same type
- PAX8 c.*290G>A Uncertain significance ★★ same type
- PAX8 c.*845G>A Uncertain significance ★★ same type
- PAX8 p.Gln354Glu Uncertain significance ★★ ⚠ same type
- PAX8 p.Gly11Arg Uncertain significance ★★ ⚠ same type
- PAX8 p.Leu266Ser Uncertain significance ★★ ⚠ same type
- PAX8 p.Met102Ile 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/pax8-p-pro25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown