Is VPS51 p.Arg433Pro (c.1298G>C) pathogenic?

VPS51 p.Arg433Pro (c.1298G>C) is classified Uncertain significance in VPS51 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely benign (0.2063); Absent from gnomAD v4.1.

How common is VPS51 p.Arg433Pro (c.1298G>C) in the general population?

VPS51 p.Arg433Pro (c.1298G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VPS51 p.Arg433Pro (c.1298G>C)?

AlphaMissense predicts likely benign (score 0.2063) — an in-silico prediction, not a clinical call.

VPS51 p.Arg433Pro

c.1298G>C · rs1947864847 · VCV2541120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2063 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2063	likely benign
REVEL	0.517	indeterminate
SaProt	LLR -5.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.0014 · regional, not allelic
Overall
CADD	25.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VPS51
Protein: p.Arg433Pro
Coding: c.1298G>C
MANE Select: NM_013265
dbSNP: rs1947864847
Type: single nucleotide variant
Location: chr11:65108769 (GRCh38)
Gene constraint: LOEUF 1.284 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.07 · 1 PDB

Full VPS51 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VPS51 p.Ala357Val Uncertain significance ★★ ⚠ same type
VPS51 p.Arg240His Uncertain significance ★★ ⚠ same type
VPS51 p.Pro11Leu Uncertain significance ★★ ⚠ same type
VPS51 c.1443+4C>T Benign/Likely benign ★★ same type
VPS51 c.1444-12C>T Benign ★★ same type
VPS51 c.1879-7C>T Benign ★★ same type
VPS51 p.Ser218= Likely benign ★★ same type
VPS51 p.Arg490Cys 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/vps51-p-arg433pro (accessed [today's date]).

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