Is AVP p.Leu73Pro (c.218T>C) pathogenic?

AVP p.Leu73Pro (c.218T>C) is classified Uncertain significance in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: ambiguous (0.5603); Absent from gnomAD v4.1; Associated with neurohypophyseal diabetes insipidus.

What condition is associated with AVP p.Leu73Pro (c.218T>C)?

AVP p.Leu73Pro (c.218T>C) is associated with neurohypophyseal diabetes insipidus (ClinVar).

How common is AVP p.Leu73Pro (c.218T>C) in the general population?

AVP p.Leu73Pro (c.218T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVP p.Leu73Pro (c.218T>C)?

AlphaMissense predicts ambiguous (score 0.5603) — an in-silico prediction, not a clinical call.

AVP p.Leu73Pro

c.218T>C · rs2517100396 · VCV2439449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5603 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,561,088)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

neurohypophyseal diabetes insipidus

Computational evidence

Protein change
AlphaMissense	0.5603	ambiguous
REVEL	0.689	pathogenic-leaning
SaProt	LLR -12.81	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.9, phastCons 1
Overall
CADD	22.0	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

No allele count reported in gnomAD v4.1 (AN 1,561,088). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AVP
Protein: p.Leu73Pro
Coding: c.218T>C
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs2517100396
Type: single nucleotide variant
Location: chr20:3083081 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 73: the pyrin domain; an α-helix; a disulfide bond

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

Disease context

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

Similar variants

NLRP3 p.Phe73= Likely benign ★★ same residue
AVP p.Ala19Thr Pathogenic ★★ ⚠ same condition
AVP p.Cys92Tyr Likely pathogenic ★★ same condition
AVP p.Gly54Arg Pathogenic ★★ same condition
AVP p.Gly96Asp Pathogenic/Likely pathogenic ★★ same condition
AVP p.Ser87Phe Pathogenic/Likely pathogenic ★★ same condition
AVP c.322+4C>A Uncertain significance ★★ same condition
AVP p.Ala141Val 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/avp-p-leu73pro (accessed [today's date]).

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