Is AVPR2 p.Pro322Thr (c.964C>A) pathogenic?

AVPR2 p.Pro322Thr (c.964C>A) is classified Likely pathogenic in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). AlphaMissense: likely pathogenic (0.885); Absent from gnomAD v4.1; Associated with nephrogenic diabetes insipidus.

What condition is associated with AVPR2 p.Pro322Thr (c.964C>A)?

AVPR2 p.Pro322Thr (c.964C>A) is associated with nephrogenic diabetes insipidus (ClinVar).

How common is AVPR2 p.Pro322Thr (c.964C>A) in the general population?

AVPR2 p.Pro322Thr (c.964C>A) 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.Pro322Thr (c.964C>A)?

AlphaMissense predicts likely pathogenic (score 0.885) — an in-silico prediction, not a clinical call.

AVPR2 p.Pro322Thr

c.964C>A · rs2148515160 · VCV1700646

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.885 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,201,965)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrogenic diabetes insipidus

Computational evidence

Protein change
AlphaMissense	0.885	likely pathogenic ✓ concordant with ClinVar
REVEL	0.993	strongly pathogenic-leaning
SaProt	LLR -13.44	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	26.3	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

No allele count reported in gnomAD v4.1 (AN 1,201,965). 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.Pro322Thr
Coding: c.964C>A
MANE Select: NM_000054
dbSNP: rs2148515160
Type: single nucleotide variant
Location: chrX:153906576 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 322: a UniProt-annotated variant site (in ndi1); 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.Pro322Leu Pathogenic/Likely pathogenic ★★ same residue
AVPR2 p.Pro322Ser Pathogenic ★ same residue
AVPR2 p.Pro322= Likely benign ★ same residue
AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
AVPR2 p.Arg137His 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

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-pro322thr (accessed [today's date]).

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