Is AVPR2 p.Arg251fs (c.752_758del) pathogenic?

AVPR2 p.Arg251fs (c.752758del) is classified Likely pathogenic in AVPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-30). Absent from gnomAD; Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Arg251fs (c.752_758del)?

AVPR2 p.Arg251fs (c.752_758del) is associated with diabetes insipidus, nephrogenic, X-linked, nephrogenic syndrome of inappropriate antidiuresis, nephrogenic diabetes insipidus (ClinVar).

How common is AVPR2 p.Arg251fs (c.752_758del) in the general population?

AVPR2 p.Arg251fs (c.752_758del) is absent from gnomAD (gnomAD).

How is Arginine vasopressin resistance inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AVPR2 p.Arg251fs

c.752_758del · rs193922118 · VCV35744

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

diabetes insipidus, nephrogenic, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.53	GERP -3.7, phastCons 0.45

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AVPR2
Protein: p.Arg251fs
Coding: c.752_758del
MANE Select: NM_000054
dbSNP: rs193922118
Type: Deletion
Location: chrX:153906254 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 251: the 'disordered' region

Full AVPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

diabetes insipidus, nephrogenic, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephrogenic syndrome of inappropriate antidiuresis nephrogenic diabetes insipidus

For 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.Arg158fs Pathogenic/Likely pathogenic ★★ same condition
AVPR2 p.Arg247fs Pathogenic ★★ same condition
AVPR2 p.Gly185fs Pathogenic/Likely pathogenic ★★ same condition
AVPR2 p.Gly257fs Likely pathogenic ★★ same condition
AVPR2 p.Ile46fs Pathogenic ★★ same condition
AVPR2 p.Tyr128del Pathogenic/Likely pathogenic ★★ same condition
AVPR2 p.Tyr205fs Pathogenic ★★ same condition
AVPR2 p.Val51fs 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-arg251fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown