Is AVPR2 p.Ala305Thr (c.913G>A) pathogenic?

AVPR2 p.Ala305Thr (c.913G>A) is classified Conflicting classifications of pathogenicity in AVPR2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.088); Rare (popmax 0.181%, afr).

How common is AVPR2 p.Ala305Thr (c.913G>A) in the general population?

AVPR2 p.Ala305Thr (c.913G>A) is rare (popmax 0.181%, afr) (gnomAD).

What do computational predictors say about AVPR2 p.Ala305Thr (c.913G>A)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

AVPR2 p.Ala305Thr

c.913G>A · rs145953185 · VCV1343590

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.50	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 3.4	GERP -3.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	9.733	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 0.181% African / African-American · 104/57,304 alleles

Filtering AF 0.153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.143%

Overall 0.00969% 117/1,206,874 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.181%	551
Admixed American	0.0175%	5,703
Remaining individualsnot grpmax-eligible	0.00843%	11,862
South Asian	0.00179%	56,018

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.Ala305Thr
Coding: c.913G>A
MANE Select: NM_000054
dbSNP: rs145953185
Type: single nucleotide variant
Location: chrX:153906525 (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.Ala305Glu Uncertain significance ★ ⚠ same residue
AVPR2 p.Ala305= Likely benign ★ same residue
AVPR2 p.Ala305Val 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

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-ala305thr (accessed [today's date]).

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