Is AVPR2 p.Gln225Pro (c.674A>C) pathogenic?

AVPR2 p.Gln225Pro (c.674A>C) is classified Uncertain significance in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-09). AlphaMissense: likely pathogenic (0.7512); Absent from gnomAD v4.1.

How common is AVPR2 p.Gln225Pro (c.674A>C) in the general population?

AVPR2 p.Gln225Pro (c.674A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVPR2 p.Gln225Pro (c.674A>C)?

AlphaMissense predicts likely pathogenic (score 0.7512) — an in-silico prediction, not a clinical call.

AVPR2 p.Gln225Pro

c.674A>C · rs2148514753 · VCV1386192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7512 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7512	likely pathogenic
REVEL	0.4	indeterminate
SaProt	LLR -14.22	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Gln225Pro
Coding: c.674A>C
MANE Select: NM_000054
dbSNP: rs2148514753
Type: single nucleotide variant
Location: chrX:153906180 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 225: an α-helix

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

Similar variants

AVPR2 p.Gln225Ter Likely 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-gln225pro (accessed [today's date]).

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