Is AVPR2 p.Val279= (c.837C>G) pathogenic?

AVPR2 p.Val279= (c.837C>G) is classified Uncertain significance in AVPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-29). Very rare (popmax 0.00123%, nfe); Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Val279= (c.837C>G)?

AVPR2 p.Val279= (c.837C>G) is associated with diabetes insipidus, nephrogenic, X-linked, nephrogenic syndrome of inappropriate antidiuresis (ClinVar).

How common is AVPR2 p.Val279= (c.837C>G) in the general population?

AVPR2 p.Val279= (c.837C>G) is very rare (popmax 0.00123%, nfe) (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.Val279=

c.837C>G · rs781801367 · VCV914620

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00123%, nfe)

Conditions

diabetes insipidus, nephrogenic, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP 0.77, phastCons 0.027
Overall
CADD	2.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00123% European (non-Finnish) · 11/895,318 alleles

Filtering AF 0.000659% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000482%

Overall 0.000909% 11/1,210,674 alleles · very rare exomes 10/1,098,218 · genomes 1/112,456 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AVPR2
Protein: p.Val279=
Coding: c.837C>G
MANE Select: NM_000054
dbSNP: rs781801367
Type: single nucleotide variant
Location: chrX:153906343 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 279: an α-helix

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.Val279del Pathogenic/Likely pathogenic ★★ same residue
AVPR2 p.Val279Ile Uncertain significance ★ ⚠ 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-val279 (accessed [today's date]).

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