Is AVPR2 p.Leu111Pro (c.332T>C) pathogenic?

AVPR2 p.Leu111Pro (c.332T>C) is classified Uncertain significance in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: ambiguous (0.4862); Absent from gnomAD v4.1.

How common is AVPR2 p.Leu111Pro (c.332T>C) in the general population?

AVPR2 p.Leu111Pro (c.332T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVPR2 p.Leu111Pro (c.332T>C)?

AlphaMissense predicts ambiguous (score 0.4862) — an in-silico prediction, not a clinical call.

AVPR2 p.Leu111Pro

c.332T>C · rs2521153625 · VCV2835082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4862 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4862	ambiguous
REVEL	0.65	pathogenic-leaning
SaProt	LLR -12.59	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	25.4	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

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.Leu111Pro
Coding: c.332T>C
MANE Select: NM_000054
dbSNP: rs2521153625
Type: single nucleotide variant
Location: chrX:153905838 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 111: an α-helix

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

Similar variants

AVPR2 p.Leu111fs Pathogenic ★ same residue
AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
AVPR2 p.Arg113Trp Pathogenic ★★ same type
AVPR2 p.Arg137Cys Pathogenic ★★ same type
AVPR2 p.Arg137His Pathogenic ★★ same type
AVPR2 p.Arg181Cys Pathogenic ★★ same type
AVPR2 p.Arg202Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
AVPR2 p.Arg337Ter Pathogenic ★★ same type

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-leu111pro (accessed [today's date]).

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