AVPR2 p.Leu274Pro
c.821T>C · VCV3338811
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9245 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9245 | likely pathogenic ✓ concordant with ClinVar · top 9% in AVPR2 |
|---|---|---|
| REVEL | 0.574 | indeterminate |
| SaProt | LLR -13.78 | damaging |
| ⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic |
| Overall | ||
| CADD | 24.2 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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.Leu274Pro
- Coding
- c.821T>C
- MANE Select
- NM_000054
- Type
- single nucleotide variant
- Location
- chrX:153906327 (GRCh38)
- Structure
- AlphaFold pLDDT 76.84 · 44 PDB
- Residue 274
- an α-helix
Similar variants
- AVPR2 p.Leu274del Likely pathogenic ★ same residue
- AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- AVPR2 p.Arg113Trp Pathogenic ★★ same type
- AVPR2 p.Arg137Cys Pathogenic ★★ same type
- AVPR2 p.Arg137His Pathogenic ★★ same type
- AVPR2 p.Arg181Cys Pathogenic ★★ ⚠ same type
- AVPR2 p.Arg202Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- AVPR2 p.Arg337Ter Pathogenic ★★ 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/avpr2-p-leu274pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown