Is AVP p.Pro43Ala (c.127C>G) pathogenic?

AVP p.Pro43Ala (c.127C>G) is classified Benign/Likely benign in AVP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0851); Rare (popmax 0.388%, eas); Associated with Inborn genetic diseases.

What condition is associated with AVP p.Pro43Ala (c.127C>G)?

AVP p.Pro43Ala (c.127C>G) is associated with Inborn genetic diseases, neurohypophyseal diabetes insipidus (ClinVar).

How common is AVP p.Pro43Ala (c.127C>G) in the general population?

AVP p.Pro43Ala (c.127C>G) is rare (popmax 0.388%, eas) (gnomAD).

What do computational predictors say about AVP p.Pro43Ala (c.127C>G)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

AVP p.Pro43Ala

c.127C>G · rs539928673 · VCV1630379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.388%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.545	indeterminate
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Overall
CADD	23.3	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

Grpmax group 0.388% East Asian · 138/35,600 alleles

Filtering AF 0.335% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.315%

Overall 0.0132% 197/1,493,928 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.388%	258
Remaining individualsnot grpmax-eligible	0.0863%	1,158
South Asian	0.00872%	11,465
Admixed American	0.00429%	23,309

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.Pro43Ala
Coding: c.127C>G
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs539928673
Type: single nucleotide variant
Location: chr20:3083172 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 43: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurohypophyseal diabetes insipidus

Similar variants

AVP p.Pro43His Uncertain significance ★ ⚠ same residue
AVP p.Pro43Leu Uncertain significance ★ ⚠ same residue
AVP p.Pro43Thr Uncertain significance ★ ⚠ same residue
NLRP3 p.Gln43Ter Uncertain significance ★ same residue
NLRP3 p.Gln43= Likely benign ★ same residue
AVP p.Ala19Thr Pathogenic ★★ ⚠ same condition
AVP p.Cys92Tyr Likely pathogenic ★★ same condition
AVP p.Gly54Arg Pathogenic ★★ 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-pro43ala (accessed [today's date]).

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