Is AVPR2 p.Ser357Phe (c.1070C>T) pathogenic?

AVPR2 p.Ser357Phe (c.1070C>T) is classified Conflicting classifications of pathogenicity in AVPR2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1913); Ultra-rare (popmax 0.0157%, afr); Associated with Inborn genetic diseases.

What condition is associated with AVPR2 p.Ser357Phe (c.1070C>T)?

AVPR2 p.Ser357Phe (c.1070C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AVPR2 p.Ser357Phe (c.1070C>T) in the general population?

AVPR2 p.Ser357Phe (c.1070C>T) is ultra-rare (popmax 0.0157%, afr) (gnomAD).

What do computational predictors say about AVPR2 p.Ser357Phe (c.1070C>T)?

AlphaMissense predicts likely benign (score 0.1913) — an in-silico prediction, not a clinical call.

AVPR2 p.Ser357Phe

c.1070C>T · rs782201621 · VCV2547230

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1913	likely benign
REVEL	0.418	indeterminate
SaProt	LLR -9.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	24.0	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 0.0157% African / African-American · 9/57,440 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00601%

Overall 0.000743% 9/1,210,709 alleles · ultra-rare

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.Ser357Phe
Coding: c.1070C>T
MANE Select: NM_000054
dbSNP: rs782201621
Type: single nucleotide variant
Location: chrX:153906682 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 357: the 'disordered' region; a modified residue (phosphoserine)

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.Ser357= Likely benign ★★ 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-ser357phe (accessed [today's date]).

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