Is AVPR2 p.Arg344Gln (c.1031G>A) pathogenic?

AVPR2 p.Arg344Gln (c.1031G>A) is classified Conflicting classifications of pathogenicity in AVPR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-07-10). AlphaMissense: likely benign (0.1023); Ultra-rare (popmax 0.0623%, eas); Associated with Inborn genetic diseases.

What condition is associated with AVPR2 p.Arg344Gln (c.1031G>A)?

AVPR2 p.Arg344Gln (c.1031G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AVPR2 p.Arg344Gln (c.1031G>A) in the general population?

AVPR2 p.Arg344Gln (c.1031G>A) is ultra-rare (popmax 0.0623%, eas) (gnomAD).

What do computational predictors say about AVPR2 p.Arg344Gln (c.1031G>A)?

AlphaMissense predicts likely benign (score 0.1023) — an in-silico prediction, not a clinical call.

AVPR2 p.Arg344Gln

c.1031G>A · rs368996823 · VCV1696254

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1023 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0623%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1023	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -8.55	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 -1.1	GERP -3.4
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	2.397	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 0.0623% East Asian · 21/33,710 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.0142% 171/1,207,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0623%	1,605
European (non-Finnish)	0.0153%	6,515
Admixed American	0.0109%	9,157
South Asian	0.00706%	14,156
Remaining individualsnot grpmax-eligible	0.00633%	15,803
Finnishnot grpmax-eligible	0.00214%	46,694

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.Arg344Gln
Coding: c.1031G>A
MANE Select: NM_000054
dbSNP: rs368996823
Type: single nucleotide variant
Location: chrX:153906643 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB

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.Arg344Trp 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-arg344gln (accessed [today's date]).

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