Is AVPR2 p.Thr7Ser (c.19A>T) pathogenic?

AVPR2 p.Thr7Ser (c.19A>T) is classified Benign in AVPR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0827); Common (popmax 8.21%, afr) — too common for a highly-penetrant pathogenic allele; Associated with diabetes insipidus, nephrogenic, X-linked.

What condition is associated with AVPR2 p.Thr7Ser (c.19A>T)?

AVPR2 p.Thr7Ser (c.19A>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.

What do computational predictors say about AVPR2 p.Thr7Ser (c.19A>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

AVPR2 p.Thr7Ser

Q: How common is AVPR2 p.Thr7Ser (c.19A>T) in the general population?

AVPR2 p.Thr7Ser (c.19A>T) is common (popmax 8.21%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.19A>T · rs5196 · VCV368071

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.21%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

diabetes insipidus, nephrogenic, X-linked

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.39	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 0.14	GERP -1.8
Regional constraint	o/e 0.80	unconstrained · MANE · 1,579 bp · p 0.00022 · regional, not allelic
Overall
CADD	0.449	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 8.21% African / African-American · 4,689/57,134 alleles

Filtering AF 8.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.93%

Overall 0.544% 6,582/1,209,863 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.21%	12
Ashkenazi Jewishnot grpmax-eligible	0.831%	120
Remaining individualsnot grpmax-eligible	0.782%	128
Admixed American	0.649%	154
Middle Eastern	0.232%	432
European (non-Finnish)	0.113%	888
South Asian	0.0246%	4,059
Finnishnot grpmax-eligible	0.0128%	7,790
East Asian	0.00593%	16,862

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.Thr7Ser
Coding: c.19A>T
MANE Select: NM_000054
dbSNP: rs5196
Type: single nucleotide variant
Location: chrX:153905164 (GRCh38)
Structure: AlphaFold pLDDT 76.84 · 44 PDB
Residue 7: the 'disordered' region; a UniProt-annotated variant site (in)

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-thr7ser (accessed [today's date]).

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