Is AVPR2 p.Arg230Gln (c.689G>A) pathogenic?

AVPR2 p.Arg230Gln (c.689G>A) is classified Conflicting classifications of pathogenicity in AVPR2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-13). AlphaMissense: likely benign (0.1213); Ultra-rare (popmax 0.0413%, amr); Associated with Inborn genetic diseases.

What condition is associated with AVPR2 p.Arg230Gln (c.689G>A)?

AVPR2 p.Arg230Gln (c.689G>A) is associated with Inborn genetic diseases, nephrogenic syndrome of inappropriate antidiuresis, diabetes insipidus, nephrogenic, X-linked (ClinVar).

How common is AVPR2 p.Arg230Gln (c.689G>A) in the general population?

AVPR2 p.Arg230Gln (c.689G>A) is ultra-rare (popmax 0.0413%, amr) (gnomAD).

What do computational predictors say about AVPR2 p.Arg230Gln (c.689G>A)?

AlphaMissense predicts likely benign (score 0.1213) — an in-silico prediction, not a clinical call.

AVPR2 p.Arg230Gln

c.689G>A · rs782608859 · VCV3132443

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1213 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1213	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -9.69	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 5.7	GERP -2.4, phastCons 0.99
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.0413% Admixed American · 19/45,970 alleles

Filtering AF 0.027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0225%

Overall 0.00537% 65/1,211,127 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0413%	2,419
Middle Eastern	0.0229%	4,373
East Asian	0.0207%	4,827
Remaining individualsnot grpmax-eligible	0.0063%	15,874
African / African-American	0.00521%	19,180
European (non-Finnish)	0.00357%	27,981

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.Arg230Gln
Coding: c.689G>A
MANE Select: NM_000054
dbSNP: rs782608859
Type: single nucleotide variant
Location: chrX:153906195 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 230: an α-helix

Full AVPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephrogenic syndrome of inappropriate antidiuresis diabetes insipidus, nephrogenic, X-linked

Similar variants

AVPR2 p.Arg230= Likely benign ★ 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-arg230gln (accessed [today's date]).

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