Is AVPR2 p.Leu97Pro (c.290T>C) pathogenic?

AVPR2 p.Leu97Pro (c.290T>C) is classified Likely pathogenic in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2011-08-18). AlphaMissense: likely pathogenic (0.9664); Absent from gnomAD v4.1; Associated with nephrogenic diabetes insipidus.

What condition is associated with AVPR2 p.Leu97Pro (c.290T>C)?

AVPR2 p.Leu97Pro (c.290T>C) is associated with nephrogenic diabetes insipidus (ClinVar).

How common is AVPR2 p.Leu97Pro (c.290T>C) in the general population?

AVPR2 p.Leu97Pro (c.290T>C) 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.

What do computational predictors say about AVPR2 p.Leu97Pro (c.290T>C)?

AlphaMissense predicts likely pathogenic (score 0.9664) — an in-silico prediction, not a clinical call.

AVPR2 p.Leu97Pro

c.290T>C · rs193922113 · VCV35738

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9664 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrogenic diabetes insipidus

Computational evidence

Protein change
AlphaMissense	0.9664	likely pathogenic ✓ concordant with ClinVar · top 4% in AVPR2
REVEL	0.65	pathogenic-leaning
SaProt	LLR -15.18	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	25.5	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.Leu97Pro
Coding: c.290T>C
MANE Select: NM_000054
dbSNP: rs193922113
Type: single nucleotide variant
Location: chrX:153905796 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 97: an α-helix

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

Disease context

nephrogenic diabetes insipidus — 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.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
AVPR2 p.Arg137His Pathogenic ★★ same condition
AVPR2 p.Pro322Leu Pathogenic/Likely pathogenic ★★ same condition
AVPR2 p.Tyr205Cys Pathogenic/Likely pathogenic ★★ same condition
AVPR2 p.Ala285Pro Likely pathogenic ★ same condition
AVPR2 p.Arg137Gly Likely pathogenic ★ same condition
AVPR2 p.Asn321Lys Likely pathogenic ★ same condition
AVPR2 p.Gln225Ter 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-leu97pro (accessed [today's date]).

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