Is AVPR2 p.Tyr128Ser (c.383A>C) pathogenic?

AVPR2 p.Tyr128Ser (c.383A>C) is classified Pathogenic/Likely pathogenic in AVPR2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). AlphaMissense: likely pathogenic (0.6539); Absent from gnomAD v4.1; Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Tyr128Ser (c.383A>C)?

AVPR2 p.Tyr128Ser (c.383A>C) is associated with diabetes insipidus, nephrogenic, X-linked, nephrogenic syndrome of inappropriate antidiuresis (ClinVar).

How common is AVPR2 p.Tyr128Ser (c.383A>C) in the general population?

AVPR2 p.Tyr128Ser (c.383A>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.Tyr128Ser (c.383A>C)?

AlphaMissense predicts likely pathogenic (score 0.6539) — an in-silico prediction, not a clinical call.

AVPR2 p.Tyr128Ser

c.383A>C · rs781950164 · VCV585474

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.6539 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

diabetes insipidus, nephrogenic, X-linked

Computational evidence

Protein change
AlphaMissense	0.6539	likely pathogenic ✓ concordant with ClinVar
REVEL	0.638	indeterminate
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	25.3	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

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.Tyr128Ser
Coding: c.383A>C
MANE Select: NM_000054
dbSNP: rs781950164
Type: single nucleotide variant
Location: chrX:153905889 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 128: 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

Also linked: nephrogenic syndrome of inappropriate antidiuresis

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.Tyr128del Pathogenic/Likely pathogenic ★★ same residue
AVPR2 p.Tyr128Cys Likely pathogenic ★ same residue
AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
AVPR2 p.Arg113Trp Pathogenic ★★ same condition
AVPR2 p.Arg137Cys Pathogenic ★★ same condition
AVPR2 p.Arg137His Pathogenic ★★ same condition
AVPR2 p.Arg181Cys Pathogenic ★★ ⚠ same condition
AVPR2 p.Arg202Cys Pathogenic/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-tyr128ser (accessed [today's date]).

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