Is AVPR2 p.Ser331= (c.993C>T) pathogenic?

AVPR2 p.Ser331= (c.993C>T) is classified Benign in AVPR2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 18.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Ser331= (c.993C>T)?

AVPR2 p.Ser331= (c.993C>T) is associated with diabetes insipidus, nephrogenic, X-linked (ClinVar).

How is Arginine vasopressin resistance inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AVPR2 p.Ser331=

Q: How common is AVPR2 p.Ser331= (c.993C>T) in the general population?

AVPR2 p.Ser331= (c.993C>T) is common (popmax 18.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.993C>T · rs5202 · VCV254776

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 18.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

diabetes insipidus, nephrogenic, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.237	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.6
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.3% African / African-American · 10,426/57,121 alleles

Filtering AF 18% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.8%

Overall 3.35% 40,172/1,200,046 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	18.3%	5
Admixed American	9%	11
Middle Eastern	6.03%	17
South Asian	5.51%	18
East Asian	4.02%	25
Remaining individualsnot grpmax-eligible	3.61%	28
Amishnot grpmax-eligible	2.2%	45
Finnishnot grpmax-eligible	2.04%	49
European (non-Finnish)	2.02%	49
Ashkenazi Jewishnot grpmax-eligible	1.69%	59

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.Ser331=
Coding: c.993C>T
MANE Select: NM_000054
dbSNP: rs5202
Type: single nucleotide variant
Location: chrX:153906605 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 331: an α-helix

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

Disease context

diabetes insipidus, nephrogenic, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Arginine vasopressin resistance (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AVPR2 p.Arg104Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
AVPR2 p.Arg113Trp Pathogenic ★★ same condition
AVPR2 p.Arg137His Pathogenic ★★ same condition
AVPR2 p.Arg181Cys Pathogenic ★★ ⚠ same condition
AVPR2 p.Arg202Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
AVPR2 p.Arg337Ter Pathogenic ★★ same condition
AVPR2 p.Asp85Asn Pathogenic ★★ same condition
AVPR2 p.Gly107Glu Likely pathogenic ★★ 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-ser331 (accessed [today's date]).

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