Is AVP p.Pro7Leu (c.20C>T) pathogenic?

AVP p.Pro7Leu (c.20C>T) is classified Pathogenic in AVP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2004-09-01). AlphaMissense: likely benign (0.0958); Absent from gnomAD v4.1; Associated with Diabetes insipidus, neurohypophyseal, autosomal recessive.

What condition is associated with AVP p.Pro7Leu (c.20C>T)?

AVP p.Pro7Leu (c.20C>T) is associated with Diabetes insipidus, neurohypophyseal, autosomal recessive (ClinVar).

How common is AVP p.Pro7Leu (c.20C>T) in the general population?

AVP p.Pro7Leu (c.20C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVP p.Pro7Leu (c.20C>T)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

AVP p.Pro7Leu

c.20C>T · rs121964892 · VCV12219

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Diabetes insipidus, neurohypophyseal, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign ⚠ discordant with ClinVar
REVEL	0.235	benign-leaning
SaProt	LLR -2.16	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 3.3	GERP 0.07, phastCons 1
Overall
CADD	16.87	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AVP
Protein: p.Pro7Leu
Coding: c.20C>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs121964892
Type: single nucleotide variant
Location: chr20:3084655 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 7: the pyrin domain; an α-helix

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

Disease context

Diabetes insipidus, neurohypophyseal, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AVP p.Pro7= Likely benign ★ same residue
AVP p.Ala19Thr Pathogenic ★★ ⚠ same type
AVP p.Cys92Tyr Likely pathogenic ★★ same type
AVP p.Glu108Ter Pathogenic ★★ same type
AVP p.Gly54Arg Pathogenic ★★ same type
AVP p.Gly96Asp Pathogenic/Likely pathogenic ★★ same type
AVP p.Ser87Phe Pathogenic/Likely pathogenic ★★ same type
NLRP3 p.Ala352Thr Likely 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/avp-p-pro7leu (accessed [today's date]).

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