Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.495%, eas)
Conditions
1
diabetes insipidus, nephrogenic, X-linked
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 -2.1 | GERP -2.8 |
| Overall | ||
| CADD | 5.779 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.495%
East Asian · 167/33,766 alleles
Filtering AF
0.433%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.41%
Overall
0.015%
182/1,210,283 alleles · rare
exomes 160/1,096,904 · genomes 22/113,379 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.495% | 202 |
| Middle Eastern | 0.0233% | 4,290 |
| Remaining individualsnot grpmax-eligible | 0.0168% | 5,947 |
| African / African-American | 0.00347% | 28,842 |
| European (non-Finnish) | 0.000447% | 223,759 |
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
- AVPR2
- Protein
- p.Ala42=
- Coding
- c.126G>A
- MANE Select
- NM_000054
- dbSNP
- rs2234695
- Type
- single nucleotide variant
- Location
- chrX:153905632 (GRCh38)
- Structure
- AlphaFold pLDDT 76.84 · 44 PDB
- Residue 42
- an α-helix; a UniProt-annotated variant site (in)
Disease context
diabetes insipidus, nephrogenic, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Arginine vasopressin resistance (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, X-linked recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- AVPR2 p.Ala42Val Benign ★★ same residue
- AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AVPR2 p.Arg113Trp Pathogenic ★★ same condition
- AVPR2 p.Arg137His Pathogenic ★★ same condition
- AVPR2 p.Arg181Cys Pathogenic ★★ same condition
- AVPR2 p.Arg202Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AVPR2 p.Arg337Ter Pathogenic ★★ same condition
- AVPR2 p.Asp85Asn 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-ala42 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown