Is AVP p.Cys92Phe (c.275G>T) pathogenic?

AVP p.Cys92Phe (c.275G>T) is classified Uncertain significance in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely pathogenic (0.9134); Absent from gnomAD v4.1.

How common is AVP p.Cys92Phe (c.275G>T) in the general population?

AVP p.Cys92Phe (c.275G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AVP p.Cys92Phe (c.275G>T)?

AlphaMissense predicts likely pathogenic (score 0.9134) — an in-silico prediction, not a clinical call.

AVP p.Cys92Phe

c.275G>T · rs121964891 · VCV2804341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9134 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,548,518)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9134	likely pathogenic · top 7% in AVP
REVEL	0.949	strongly pathogenic-leaning
SaProt	LLR -13.03	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 7.2	GERP 1.7, phastCons 1
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 1,548,518). 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.Cys92Phe
Coding: c.275G>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs121964891
Type: single nucleotide variant
Location: chr20:3083024 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 92: the pyrin domain; a disulfide bond

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

Similar variants

AVP p.Cys92Tyr Likely pathogenic ★★ same residue
AVP p.Ala19Thr 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
NLRP3 p.Ala352Val Pathogenic/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-cys92phe (accessed [today's date]).

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