Is AVPR2 p.Ala305Val (c.914C>T) pathogenic?

AVPR2 p.Ala305Val (c.914C>T) is classified Likely benign in AVPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1067); Ultra-rare (popmax 0.0454%, afr).

How common is AVPR2 p.Ala305Val (c.914C>T) in the general population?

AVPR2 p.Ala305Val (c.914C>T) is ultra-rare (popmax 0.0454%, afr) (gnomAD).

What do computational predictors say about AVPR2 p.Ala305Val (c.914C>T)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

AVPR2 p.Ala305Val

c.914C>T · rs138974323 · VCV2072798

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0454%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	12.6	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 0.0454% African / African-American · 26/57,248 alleles

Filtering AF 0.0318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0272%

Overall 0.00447% 54/1,206,773 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0454%	2,202
East Asian	0.00889%	11,245
Admixed American	0.00658%	15,199
Remaining individualsnot grpmax-eligible	0.00632%	15,812
South Asian	0.00536%	18,671
European (non-Finnish)	0.00179%	55,841

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.Ala305Val
Coding: c.914C>T
MANE Select: NM_000054
dbSNP: rs138974323
Type: single nucleotide variant
Location: chrX:153906526 (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.Ala305Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
AVPR2 p.Ala305= 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-ala305val (accessed [today's date]).

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