Is AVP p.Cys44Phe (c.131G>T) pathogenic?

AVP p.Cys44Phe (c.131G>T) is classified Likely pathogenic in AVP (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9703); Absent from gnomAD v4.1; Associated with neurohypophyseal diabetes insipidus.

What condition is associated with AVP p.Cys44Phe (c.131G>T)?

AVP p.Cys44Phe (c.131G>T) is associated with neurohypophyseal diabetes insipidus (ClinVar).

How common is AVP p.Cys44Phe (c.131G>T) in the general population?

AVP p.Cys44Phe (c.131G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVP p.Cys44Phe (c.131G>T)?

AlphaMissense predicts likely pathogenic (score 0.9703) — an in-silico prediction, not a clinical call.

AVP p.Cys44Phe

c.131G>T · rs1057516192 · VCV369949

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9703 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,496,980)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurohypophyseal diabetes insipidus

Computational evidence

Protein change
AlphaMissense	0.9703	likely pathogenic ✓ concordant with ClinVar · top 2% in AVP
REVEL	0.943	strongly pathogenic-leaning
SaProt	LLR -12.41	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1, phastCons 1
Overall
CADD	28.5	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 1,496,980). 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.Cys44Phe
Coding: c.131G>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs1057516192
Type: single nucleotide variant
Location: chr20:3083168 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 44: 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

AVP p.Cys44= Likely benign ★★ same residue
NLRP3 p.Thr44Arg 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-cys44phe (accessed [today's date]).

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