Is AVPR2 p.Val183Met (c.547G>A) pathogenic?

AVPR2 p.Val183Met (c.547G>A) is classified Uncertain significance in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-20). AlphaMissense: likely benign (0.1979); Very rare (popmax 0.00592%, eas); Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Val183Met (c.547G>A)?

AVPR2 p.Val183Met (c.547G>A) is associated with diabetes insipidus, nephrogenic, X-linked, nephrogenic syndrome of inappropriate antidiuresis (ClinVar).

How common is AVPR2 p.Val183Met (c.547G>A) in the general population?

AVPR2 p.Val183Met (c.547G>A) is very rare (popmax 0.00592%, eas) (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.Val183Met (c.547G>A)?

AlphaMissense predicts likely benign (score 0.1979) — an in-silico prediction, not a clinical call.

AVPR2 p.Val183Met

c.547G>A · VCV3598172

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00592%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

diabetes insipidus, nephrogenic, X-linked

Computational evidence

Protein change
AlphaMissense	0.1979	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00592% East Asian · 2/33,805 alleles

Filtering AF 0.00098% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000743% 9/1,210,563 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00592%	16,903
African / African-American	0.00173%	57,716
European (non-Finnish)	0.00067%	149,239

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.Val183Met
Coding: c.547G>A
MANE Select: NM_000054
Type: single nucleotide variant
Location: chrX:153906053 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 183: a disulfide bond

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.Val183Ala 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
AVPR2 p.Arg337Ter 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-val183met (accessed [today's date]).

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