Is AVP p.Pro82Leu (c.245C>T) pathogenic?

AVP p.Pro82Leu (c.245C>T) is classified Benign in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1109); Rare (popmax 0.454%, afr).

How common is AVP p.Pro82Leu (c.245C>T) in the general population?

AVP p.Pro82Leu (c.245C>T) is rare (popmax 0.454%, afr) (gnomAD).

What do computational predictors say about AVP p.Pro82Leu (c.245C>T)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

AVP p.Pro82Leu

c.245C>T · rs5195 · VCV746584

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.454%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.598	indeterminate
SaProt	LLR -8.84	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 6.9	GERP 0.65, phastCons 1
Overall
CADD	23.8	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 0.454% African / African-American · 323/71,126 alleles

Filtering AF 0.413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.397%

Overall 0.0254% 397/1,560,994 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.454%	220
Middle Eastern	0.055%	1,818
Admixed American	0.0409%	2,446
Remaining individualsnot grpmax-eligible	0.0363%	2,757
South Asian	0.00231%	43,268
European (non-Finnish)	0.00206%	48,501

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.Pro82Leu
Coding: c.245C>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs5195
Type: single nucleotide variant
Location: chr20:3083054 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 82: the pyrin domain; an α-helix; a disulfide bond

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

Similar variants

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
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-pro82leu (accessed [today's date]).

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