Is AVP p.Ser18= (c.54C>T) pathogenic?

AVP p.Ser18= (c.54C>T) is classified Likely benign in AVP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-04). Ultra-rare (popmax 0.011%, sas); Associated with neurohypophyseal diabetes insipidus.

What condition is associated with AVP p.Ser18= (c.54C>T)?

AVP p.Ser18= (c.54C>T) is associated with neurohypophyseal diabetes insipidus (ClinVar).

How common is AVP p.Ser18= (c.54C>T) in the general population?

AVP p.Ser18= (c.54C>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

AVP p.Ser18=

c.54C>T · rs769495733 · VCV739003

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

neurohypophyseal diabetes insipidus

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -4.2
Overall
CADD	0.336	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,090 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.0039% 63/1,613,768 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,109
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00667%	15,004
European (non-Finnish)	0.00339%	29,501
African / African-American	0.00267%	37,471
East Asian	0.00223%	44,900

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: AVP
Protein: p.Ser18=
Coding: c.54C>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs769495733
Type: single nucleotide variant
Location: chr20:3084621 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 18: the pyrin domain; 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

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
AVP p.Asp35Glu 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-ser18 (accessed [today's date]).

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