Is AVPR2 p.Arg251Cys (c.751C>T) pathogenic?

AVPR2 p.Arg251Cys (c.751C>T) is classified Likely benign in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.1509); Ultra-rare (popmax 0.0118%, eas); Associated with Inborn genetic diseases.

What condition is associated with AVPR2 p.Arg251Cys (c.751C>T)?

AVPR2 p.Arg251Cys (c.751C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AVPR2 p.Arg251Cys (c.751C>T) in the general population?

AVPR2 p.Arg251Cys (c.751C>T) is ultra-rare (popmax 0.0118%, eas) (gnomAD).

What do computational predictors say about AVPR2 p.Arg251Cys (c.751C>T)?

AlphaMissense predicts likely benign (score 0.1509) — an in-silico prediction, not a clinical call.

AVPR2 p.Arg251Cys

c.751C>T · VCV3467988

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1509	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.57	GERP -2
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	4.31	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

Grpmax group 0.0118% East Asian · 4/33,782 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00157% 19/1,209,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0118%	8,446
South Asian	0.00527%	18,973
Remaining individualsnot grpmax-eligible	0.0042%	23,790
European (non-Finnish)	0.00112%	89,456

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.Arg251Cys
Coding: c.751C>T
MANE Select: NM_000054
Type: single nucleotide variant
Location: chrX:153906257 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 251: the 'disordered' region

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.Arg251His Likely benign ★ ⚠ same residue
AVPR2 p.Arg251Gly Likely benign ★★ same residue
AVPR2 p.Arg251fs Likely 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

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-arg251cys (accessed [today's date]).

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