Is AVP p.Pro153Leu (c.458C>T) pathogenic?

AVP p.Pro153Leu (c.458C>T) is classified Uncertain significance in AVP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-08). AlphaMissense: likely benign (0.1266); Very rare (popmax 0.00108%, nfe).

How common is AVP p.Pro153Leu (c.458C>T) in the general population?

AVP p.Pro153Leu (c.458C>T) is very rare (popmax 0.00108%, nfe) (gnomAD).

What do computational predictors say about AVP p.Pro153Leu (c.458C>T)?

AlphaMissense predicts likely benign (score 0.1266) — an in-silico prediction, not a clinical call.

AVP p.Pro153Leu

c.458C>T · rs2517099294 · VCV2443499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00108%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1266	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -6.63	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 3.8	GERP -1.6, phastCons 0.99
Overall
CADD	18.12	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 0.00108% European (non-Finnish) · 11/1,019,482 alleles

Filtering AF 0.000579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000423%

Overall 0.000972% 11/1,132,184 alleles · very rare

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.Pro153Leu
Coding: c.458C>T
MANE Select: NM_001243133 · reported on NM_000490
dbSNP: rs2517099294
Type: single nucleotide variant
Location: chr20:3082667 (GRCh38)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 153: the fisna domain

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

Similar variants

AVP p.Pro153Ser Uncertain significance ★ ⚠ 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-pro153leu (accessed [today's date]).

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