Is AVPR2 p.Arg64Trp (c.190C>T) pathogenic?

AVPR2 p.Arg64Trp (c.190C>T) is classified Likely benign in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-16). AlphaMissense: likely benign (0.1741); Rare (popmax 0.179%, afr).

How common is AVPR2 p.Arg64Trp (c.190C>T) in the general population?

AVPR2 p.Arg64Trp (c.190C>T) is rare (popmax 0.179%, afr) (gnomAD).

What do computational predictors say about AVPR2 p.Arg64Trp (c.190C>T)?

AlphaMissense predicts likely benign (score 0.1741) — an in-silico prediction, not a clinical call.

AVPR2 p.Arg64Trp

c.190C>T · rs150351033 · VCV716656

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1741 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.179%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1741	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -11.46	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.76, phastCons 0.91
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	20.6	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 0.179% African / African-American · 103/57,632 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.14%

Overall 0.01% 121/1,205,990 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.179%	560
Remaining individualsnot grpmax-eligible	0.0169%	5,923
Admixed American	0.00874%	11,437
European (non-Finnish)	0.000672%	148,895

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.Arg64Trp
Coding: c.190C>T
MANE Select: NM_000054
dbSNP: rs150351033
Type: single nucleotide variant
Location: chrX:153905696 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 64: an α-helix; a UniProt-annotated variant site (in ndi1); a UniProt-annotated variant site (in)

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

Similar variants

AVPR2 p.Arg64= Likely benign ★ 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-arg64trp (accessed [today's date]).

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