Is AVPR2 p.Leu131Pro (c.392T>C) pathogenic?

AVPR2 p.Leu131Pro (c.392T>C) is classified Pathogenic in AVPR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-02-04). AlphaMissense: likely pathogenic (0.8512); Absent from gnomAD v4.1; Associated with AVPR2-related disorder.

What condition is associated with AVPR2 p.Leu131Pro (c.392T>C)?

AVPR2 p.Leu131Pro (c.392T>C) is associated with AVPR2-related disorder (ClinVar).

How common is AVPR2 p.Leu131Pro (c.392T>C) in the general population?

AVPR2 p.Leu131Pro (c.392T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVPR2 p.Leu131Pro (c.392T>C)?

AlphaMissense predicts likely pathogenic (score 0.8512) — an in-silico prediction, not a clinical call.

AVPR2 p.Leu131Pro

c.392T>C · rs878853079 · VCV235612

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8512 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AVPR2-related disorder

Computational evidence

Protein change
AlphaMissense	0.8512	likely pathogenic ✓ concordant with ClinVar
REVEL	0.835	moderately pathogenic-leaning
SaProt	LLR -13.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	27.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AVPR2
Protein: p.Leu131Pro
Coding: c.392T>C
MANE Select: NM_000054
dbSNP: rs878853079
Type: single nucleotide variant
Location: chrX:153905898 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 131: an α-helix; a disulfide bond

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

Disease context

AVPR2-related disorder

Similar variants

AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
AVPR2 p.Arg113Trp Pathogenic ★★ same condition
AVPR2 p.Arg137His Pathogenic ★★ same condition
AVPR2 p.Arg337Ter Pathogenic ★★ same condition
AVPR2 p.Trp296Ter Pathogenic ★★ same condition
AVPR2 p.Trp71Ter Pathogenic ★★ same condition
AVPR2 p.Trp99Ter Pathogenic ★★ same condition
AVPR2 p.Tyr205Cys 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-leu131pro (accessed [today's date]).

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