Is AVPR2 p.Arg337Ter (c.1009C>T) pathogenic?

AVPR2 p.Arg337Ter (c.1009C>T) is classified Pathogenic in AVPR2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-08). Absent from gnomAD v4.1; Associated with AVPR2-related disorder.

What condition is associated with AVPR2 p.Arg337Ter (c.1009C>T)?

AVPR2 p.Arg337Ter (c.1009C>T) is associated with AVPR2-related disorder, nephrogenic syndrome of inappropriate antidiuresis, diabetes insipidus, nephrogenic, X-linked (ClinVar).

How common is AVPR2 p.Arg337Ter (c.1009C>T) in the general population?

AVPR2 p.Arg337Ter (c.1009C>T) is absent from gnomAD v4.1 (gnomAD).

AVPR2 p.Arg337Ter

c.1009C>T · rs104894753 · VCV10844

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,204,566)

Conditions

AVPR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,204,566). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AVPR2
Protein: p.Arg337Ter
Coding: c.1009C>T
MANE Select: NM_000054
dbSNP: rs104894753
Type: single nucleotide variant
Location: chrX:153906621 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB

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

Disease context

AVPR2-related disorder

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

Similar variants

AVPR2 p.Arg337Gln 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.Asp85Asn 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-arg337ter (accessed [today's date]).

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