Is VPS33B p.Pro191Arg (c.572C>G) pathogenic?

VPS33B p.Pro191Arg (c.572C>G) is classified Uncertain significance in VPS33B (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-19). AlphaMissense: likely benign (0.1364); Absent from gnomAD v4.1; Associated with arthrogryposis, renal dysfunction, and cholestasis 1.

What condition is associated with VPS33B p.Pro191Arg (c.572C>G)?

VPS33B p.Pro191Arg (c.572C>G) is associated with arthrogryposis, renal dysfunction, and cholestasis 1 (ClinVar).

How common is VPS33B p.Pro191Arg (c.572C>G) in the general population?

VPS33B p.Pro191Arg (c.572C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VPS33B p.Pro191Arg (c.572C>G)?

AlphaMissense predicts likely benign (score 0.1364) — an in-silico prediction, not a clinical call.

VPS33B p.Pro191Arg

c.572C>G · rs770015890 · VCV1028607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1364 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

arthrogryposis, renal dysfunction, and cholestasis 1

Computational evidence

Protein change
AlphaMissense	0.1364	likely benign
REVEL	0.551	indeterminate
SaProt	LLR -11.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.036 · regional, not allelic
Overall
CADD	23.0	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

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: VPS33B
Protein: p.Pro191Arg
Coding: c.572C>G
MANE Select: NM_018668
dbSNP: rs770015890
Type: single nucleotide variant
Location: chr15:91007500 (GRCh38)
Gene constraint: LOEUF 0.971 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.82

Full VPS33B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arthrogryposis, renal dysfunction, and cholestasis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VPS33B p.Pro191Ser Uncertain significance ★ ⚠ same residue
VPS33B c.1030+1G>A Likely pathogenic ★★ same condition
VPS33B c.1225+5G>C Pathogenic/Likely pathogenic ★★ same condition
VPS33B c.239+5G>A Pathogenic/Likely pathogenic ★★ same condition
VPS33B c.240-1G>C Pathogenic/Likely pathogenic ★★ same condition
VPS33B c.403+2T>A Pathogenic ★★ same condition
VPS33B p.Arg107Ter Pathogenic/Likely pathogenic ★★ same condition
VPS33B p.Arg438Ter Pathogenic ★★ same condition

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/vps33b-p-pro191arg (accessed [today's date]).

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