Is AVPR2 p.Val183Ala (c.548T>C) pathogenic?

AVPR2 p.Val183Ala (c.548T>C) is classified Uncertain significance in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-11). AlphaMissense: likely benign (0.1627); Very rare (popmax 0.0029%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AVPR2 p.Val183Ala (c.548T>C)?

AVPR2 p.Val183Ala (c.548T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AVPR2 p.Val183Ala (c.548T>C) in the general population?

AVPR2 p.Val183Ala (c.548T>C) is very rare (popmax 0.0029%, nfe) (gnomAD).

What do computational predictors say about AVPR2 p.Val183Ala (c.548T>C)?

AlphaMissense predicts likely benign (score 0.1627) — an in-silico prediction, not a clinical call.

AVPR2 p.Val183Ala

c.548T>C · VCV4867281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0029%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1627	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -4.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.15, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0029% European (non-Finnish) · 26/895,378 alleles

Filtering AF 0.00202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00172%

Overall 0.00215% 26/1,210,524 alleles · very rare

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.Val183Ala
Coding: c.548T>C
MANE Select: NM_000054
Type: single nucleotide variant
Location: chrX:153906054 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 183: a disulfide bond

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.Val183Met Uncertain significance ★ ⚠ 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.Pro286Leu Likely pathogenic ★ same condition
AVPR2 p.Ala114Thr 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-val183ala (accessed [today's date]).

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