Is AVP p.Ala141Val (c.422C>T) pathogenic?

AVP p.Ala141Val (c.422C>T) is classified Uncertain significance in AVP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1224); Ultra-rare (popmax 0.0496%, afr); Associated with neurohypophyseal diabetes insipidus.

What condition is associated with AVP p.Ala141Val (c.422C>T)?

AVP p.Ala141Val (c.422C>T) is associated with neurohypophyseal diabetes insipidus (ClinVar).

How common is AVP p.Ala141Val (c.422C>T) in the general population?

AVP p.Ala141Val (c.422C>T) is ultra-rare (popmax 0.0496%, afr) (gnomAD).

What do computational predictors say about AVP p.Ala141Val (c.422C>T)?

AlphaMissense predicts likely benign (score 0.1224) — an in-silico prediction, not a clinical call.

AVP p.Ala141Val

c.422C>T · rs566930108 · VCV2896713

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1224 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0496%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurohypophyseal diabetes insipidus

Computational evidence

Protein change
AlphaMissense	0.1224	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -8.23	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 3.5	GERP 0.46, phastCons 1
Overall
CADD	21.2	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 0.0496% African / African-American · 32/64,554 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00333% 43/1,290,444 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0496%	2,017
Remaining individualsnot grpmax-eligible	0.0188%	5,315
Admixed American	0.00801%	12,479

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.Ala141Val
Coding: c.422C>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs566930108
Type: single nucleotide variant
Location: chr20:3082703 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 141: an α-helix; the fisna domain

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.Ala141Thr Uncertain significance ★ ⚠ same residue
NLRP3 p.Tyr141= Benign ★★ same residue
NLRP3 p.Tyr141Ter 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

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-ala141val (accessed [today's date]).

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