Is AVPR2 p.Arg68Gln (c.203G>A) pathogenic?

AVPR2 p.Arg68Gln (c.203G>A) is classified Benign in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1052); Rare (popmax 0.506%, afr).

How common is AVPR2 p.Arg68Gln (c.203G>A) in the general population?

AVPR2 p.Arg68Gln (c.203G>A) is rare (popmax 0.506%, afr) (gnomAD).

What do computational predictors say about AVPR2 p.Arg68Gln (c.203G>A)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

AVPR2 p.Arg68Gln

c.203G>A · rs61733408 · VCV711109

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.506%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -8.64	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 2.4	GERP -3.7, phastCons 0.98
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	20.0	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 0.506% African / African-American · 292/57,745 alleles

Filtering AF 0.458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.439%

Overall 0.1% 1,213/1,209,359 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.506%	198
Finnishnot grpmax-eligible	0.199%	503
Admixed American	0.124%	808
Remaining individualsnot grpmax-eligible	0.114%	881
European (non-Finnish)	0.0799%	1,252
Middle Eastern	0.0232%	4,314
South Asian	0.00703%	14,232

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.Arg68Gln
Coding: c.203G>A
MANE Select: NM_000054
dbSNP: rs61733408
Type: single nucleotide variant
Location: chrX:153905709 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB

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

Similar variants

AVPR2 p.Arg68Trp Uncertain significance ★★ ⚠ 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-arg68gln (accessed [today's date]).

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