Is AVPR2 p.Arg247fs (c.738del) pathogenic?

AVPR2 p.Arg247fs (c.738del) is classified Pathogenic in AVPR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-22). Absent from gnomAD v4.1; Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Arg247fs (c.738del)?

AVPR2 p.Arg247fs (c.738del) is associated with diabetes insipidus, nephrogenic, X-linked (ClinVar).

How common is AVPR2 p.Arg247fs (c.738del) in the general population?

AVPR2 p.Arg247fs (c.738del) is absent from gnomAD v4.1 (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.Arg247fs

c.738del · rs781942628 · VCV10835

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,212,012)

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 -4.7	GERP -3.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,212,012). 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.Arg247fs
Coding: c.738del
MANE Select: NM_000054
dbSNP: rs781942628
Type: Deletion
Location: chrX:153906239 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 247: a UniProt-annotated variant site (in ndi1); a UniProt-annotated variant site (in a breast cancer sample; somatic mutation); 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

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.Arg247His Benign/Likely benign ★★ ⚠ same residue
AVPR2 p.Arg251fs 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.Ala114_Val115insTer Pathogenic ★ same condition
AVPR2 p.Glu198fs Pathogenic ★ same condition
AVPR2 p.Gly69fs Likely 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-arg247fs (accessed [today's date]).

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