Is AVPR2 p.Ile130Phe (c.388A>T) pathogenic?

AVPR2 p.Ile130Phe (c.388A>T) is classified Pathogenic in AVPR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-04-01). AlphaMissense: likely pathogenic (0.8715); Absent from gnomAD v4.1; Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Ile130Phe (c.388A>T)?

AVPR2 p.Ile130Phe (c.388A>T) is associated with diabetes insipidus, nephrogenic, X-linked (ClinVar).

How common is AVPR2 p.Ile130Phe (c.388A>T) in the general population?

AVPR2 p.Ile130Phe (c.388A>T) 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.Ile130Phe (c.388A>T)?

AlphaMissense predicts likely pathogenic (score 0.8715) — an in-silico prediction, not a clinical call.

AVPR2 p.Ile130Phe

c.388A>T · rs796052096 · VCV204318

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8715 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

diabetes insipidus, nephrogenic, X-linked

Computational evidence

Protein change
AlphaMissense	0.8715	likely pathogenic ✓ concordant with ClinVar
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -3.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	25.8	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.Ile130Phe
Coding: c.388A>T
MANE Select: NM_000054
dbSNP: rs796052096
Type: single nucleotide variant
Location: chrX:153905894 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 130: an α-helix; a disulfide bond; a UniProt-annotated variant site (in ndi1)

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.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
AVPR2 p.Gly107Glu 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-ile130phe (accessed [today's date]).

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