Is AVP p.Phe120Ser (c.359T>C) pathogenic?

AVP p.Phe120Ser (c.359T>C) is classified Uncertain significance in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.1242); Very rare (popmax 0.00156%, afr); Associated with neurohypophyseal diabetes insipidus.

What condition is associated with AVP p.Phe120Ser (c.359T>C)?

AVP p.Phe120Ser (c.359T>C) is associated with neurohypophyseal diabetes insipidus (ClinVar).

How common is AVP p.Phe120Ser (c.359T>C) in the general population?

AVP p.Phe120Ser (c.359T>C) is very rare (popmax 0.00156%, afr) (gnomAD).

What do computational predictors say about AVP p.Phe120Ser (c.359T>C)?

AlphaMissense predicts likely benign (score 0.1242) — an in-silico prediction, not a clinical call.

AVP p.Phe120Ser

c.359T>C · VCV3587161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1242 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00156%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurohypophyseal diabetes insipidus

Computational evidence

Protein change
AlphaMissense	0.1242	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -5.04	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 0.3	GERP -2.9
Overall
CADD	7.945	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00156% African / African-American · 1/64,008 alleles

Overall 0.000179% 2/1,116,800 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00156%	64,008
European (non-Finnish)	9.91e-05%	1,009,284

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.Phe120Ser
Coding: c.359T>C
MANE Select: NM_001243133 · reported on NM_000490
Type: single nucleotide variant
Location: chr20:3082766 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB

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.Glu120Asp Uncertain significance ★ ⚠ same residue
NLRP3 p.Glu120Ter Uncertain significance ★ 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

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-phe120ser (accessed [today's date]).

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