Is AVP p.Ala91Val (c.272C>T) pathogenic?

AVP p.Ala91Val (c.272C>T) is classified Uncertain significance in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely benign (0.0913); Absent from gnomAD v4.1.

How common is AVP p.Ala91Val (c.272C>T) in the general population?

AVP p.Ala91Val (c.272C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVP p.Ala91Val (c.272C>T)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

AVP p.Ala91Val

c.272C>T · VCV3901384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,526,402)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.347	indeterminate
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.79	donor gain · deltas
Pangolin	Δ0.57	gain · loss 0.22 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.2	GERP 0.66, phastCons 1
Overall
CADD	24.9	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

No allele count reported in gnomAD v4.1 (AN 1,526,402). 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.Ala91Val
Coding: c.272C>T
MANE Select: NM_001243133 · reported on NM_000490
Type: single nucleotide variant
Location: chr20:3083027 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 91: the pyrin domain; a disulfide bond

Full AVP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AVP p.Ala91= Likely benign ★ same residue
AVP p.Ala19Thr Pathogenic ★★ ⚠ same type
AVP p.Cys92Tyr Likely pathogenic ★★ same type
AVP p.Glu108Ter Pathogenic ★★ same type
AVP p.Gly54Arg Pathogenic ★★ same type
AVP p.Gly96Asp Pathogenic/Likely pathogenic ★★ same type
AVP p.Ser87Phe Pathogenic/Likely pathogenic ★★ same type
NLRP3 p.Ala352Thr Likely pathogenic ★★ ⚠ same type

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-ala91val (accessed [today's date]).

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