Is AVPR2 p.Pro34Leu (c.101C>T) pathogenic?

AVPR2 p.Pro34Leu (c.101C>T) is classified Conflicting classifications of pathogenicity in AVPR2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-01). AlphaMissense: likely benign (0.1241); Very rare (popmax 0.00655%, amr); Associated with Inborn genetic diseases.

What condition is associated with AVPR2 p.Pro34Leu (c.101C>T)?

AVPR2 p.Pro34Leu (c.101C>T) is associated with Inborn genetic diseases, nephrogenic syndrome of inappropriate antidiuresis, diabetes insipidus, nephrogenic, X-linked (ClinVar).

How common is AVPR2 p.Pro34Leu (c.101C>T) in the general population?

AVPR2 p.Pro34Leu (c.101C>T) is very rare (popmax 0.00655%, amr) (gnomAD).

What do computational predictors say about AVPR2 p.Pro34Leu (c.101C>T)?

AlphaMissense predicts likely benign (score 0.1241) — an in-silico prediction, not a clinical call.

AVPR2 p.Pro34Leu

c.101C>T · rs781991255 · VCV2219485

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1241 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00655%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1241	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -3.1, phastCons 0.77
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	7.44	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 0.00655% Admixed American · 3/45,817 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000881%

Overall 0.00132% 16/1,207,826 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00655%	15,272
African / African-American	0.00348%	28,758
Remaining individualsnot grpmax-eligible	0.00211%	47,434
European (non-Finnish)	0.00112%	89,401

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.Pro34Leu
Coding: c.101C>T
MANE Select: NM_000054
dbSNP: rs781991255
Type: single nucleotide variant
Location: chrX:153905607 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB

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.Pro34= 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-pro34leu (accessed [today's date]).

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