AVPR2 p.Trp296Ter
c.888G>A · rs2521160397 · VCV2812101
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
AVPR2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (3 of 4, 22 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AVPR2
- Protein
- p.Trp296Ter
- Coding
- c.888G>A
- MANE Select
- NM_000054
- dbSNP
- rs2521160397
- Type
- single nucleotide variant
- Location
- chrX:153906394 (GRCh38)
- Structure
- AlphaFold pLDDT 76.84 · 44 PDB
- Residue 296
- an α-helix
Disease context
AVPR2-related disorder
Similar variants
- AVPR2 p.Trp296Arg Uncertain significance ★ ⚠ same residue
- AVPR2 p.Trp296Leu Uncertain significance ★ ⚠ same residue
- AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AVPR2 p.Arg113Trp Pathogenic ★★ same condition
- AVPR2 p.Arg137His Pathogenic ★★ same condition
- AVPR2 p.Arg337Ter Pathogenic ★★ same condition
- AVPR2 p.Leu131Pro Pathogenic ★★ same condition
- AVPR2 p.Trp71Ter Pathogenic ★★ same condition
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/avpr2-p-trp296ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown