Is AVPR2 p.Ala361Thr (c.1081G>A) pathogenic?

AVPR2 p.Ala361Thr (c.1081G>A) is classified Likely benign in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0296%, eas).

How common is AVPR2 p.Ala361Thr (c.1081G>A) in the general population?

AVPR2 p.Ala361Thr (c.1081G>A) is ultra-rare (popmax 0.0296%, eas) (gnomAD).

What do computational predictors say about AVPR2 p.Ala361Thr (c.1081G>A)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

AVPR2 p.Ala361Thr

c.1081G>A · VCV3614650

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -6.43	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 9.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	18.35	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 0.0296% East Asian · 10/33,784 alleles

Filtering AF 0.016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00149% 18/1,210,606 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0296%	3,378
Remaining individualsnot grpmax-eligible	0.0021%	47,622
European (non-Finnish)	0.000782%	127,871

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.Ala361Thr
Coding: c.1081G>A
MANE Select: NM_000054
Type: single nucleotide variant
Location: chrX:153906693 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 361: a β-strand; the 'disordered' region

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

Similar variants

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
AVPR2 p.Asp85Asn 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-ala361thr (accessed [today's date]).

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