Is AVPR2 p.Pro286Leu (c.857C>T) pathogenic?

AVPR2 p.Pro286Leu (c.857C>T) is classified Likely pathogenic in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-29). AlphaMissense: likely pathogenic (0.8416); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AVPR2 p.Pro286Leu (c.857C>T)?

AVPR2 p.Pro286Leu (c.857C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AVPR2 p.Pro286Leu (c.857C>T) in the general population?

AVPR2 p.Pro286Leu (c.857C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVPR2 p.Pro286Leu (c.857C>T)?

AlphaMissense predicts likely pathogenic (score 0.8416) — an in-silico prediction, not a clinical call.

AVPR2 p.Pro286Leu

c.857C>T · rs1557100917 · VCV521776

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8416 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8416	likely pathogenic ✓ concordant with ClinVar
REVEL	0.943	strongly pathogenic-leaning
SaProt	LLR -13.69	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	26.8	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.Pro286Leu
Coding: c.857C>T
MANE Select: NM_000054
dbSNP: rs1557100917
Type: single nucleotide variant
Location: chrX:153906363 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 286: a UniProt-annotated variant site (in ndi1); 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

Similar variants

AVPR2 p.Pro286Ser Pathogenic ★ same residue
AVPR2 p.Pro244Thr Uncertain significance ★★ ⚠ same condition
AVPR2 p.Pro349Leu Uncertain significance ★★ ⚠ same condition
AVPR2 p.Ala223Thr Benign/Likely benign ★★ same condition
AVPR2 p.Gly257Ser Benign/Likely benign ★★ same condition
AVPR2 p.Gly352Asp Benign/Likely benign ★★ same condition
AVPR2 p.Ala114Thr Uncertain significance ★ ⚠ same condition
AVPR2 p.Ala179Thr Uncertain significance ★ ⚠ 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-pro286leu (accessed [today's date]).

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