PSENEN p.Pro83=
c.249C>T · rs377423067 · VCV1647839
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, 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 0.34 | GERP -2.5, phastCons 0.98 |
| Overall | ||
| CADD | 12.58 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/60,024 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00578%
Overall
0.000558%
9/1,614,076 alleles · ultra-rare
exomes 9/1,461,878 · genomes 0/152,198 · 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
- PSENEN
- Protein
- p.Pro83=
- Coding
- c.249C>T
- MANE Select
- NM_172341
- dbSNP
- rs377423067
- Type
- single nucleotide variant
- Location
- chr19:35746790 (GRCh38)
- Gene constraint
- LOEUF 0.552 · pLI 0.94 (gnomAD)
- Structure
- AlphaFold pLDDT 92.84 · 27 PDB
- Residue 83
- a turn
Similar variants
- PSENEN p.Ala46Asp Uncertain significance ★★ ⚠ same type
- PSENEN p.Arg82Gln Uncertain significance ★★ ⚠ same type
- PSENEN p.Arg84His Uncertain significance ★★ ⚠ same type
- PSENEN p.Gly86Cys Uncertain significance ★★ ⚠ same type
- PSENEN p.Leu43Phe Uncertain significance ★★ ⚠ same type
- PSENEN p.Pro45Ser Uncertain significance ★★ ⚠ same type
- PSENEN p.Thr100Asn Uncertain significance ★★ ⚠ same type
- PSENEN c.61+17G>C Benign/Likely 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/psenen-p-pro83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown