Is PPP3CB p.Val52Ile (c.154G>A) pathogenic?

PPP3CB p.Val52Ile (c.154G>A) is classified Uncertain significance in PPP3CB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.0957); Absent from gnomAD v4.1.

How common is PPP3CB p.Val52Ile (c.154G>A) in the general population?

PPP3CB p.Val52Ile (c.154G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPP3CB p.Val52Ile (c.154G>A)?

AlphaMissense predicts likely benign (score 0.0957) — an in-silico prediction, not a clinical call.

PPP3CB p.Val52Ile

c.154G>A · rs2495839112 · VCV2528292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0957	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -8.33	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 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 17 kb · p 0.031 · regional, not allelic
Overall
CADD	24.0	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: PPP3CB
Protein: p.Val52Ile
Coding: c.154G>A
MANE Select: NM_021132
dbSNP: rs2495839112
Type: single nucleotide variant
Location: chr10:73479449 (GRCh38)
Gene constraint: LOEUF 0.254 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.79 · 3 PDB
Residue 52: an α-helix

Full PPP3CB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPP3CB p.Ala292Ser Uncertain significance ★ ⚠ same type
PPP3CB p.Ala498Ser Uncertain significance ★ ⚠ same type
PPP3CB p.Ala510Thr Uncertain significance ★ ⚠ same type
PPP3CB p.Ala510Val Uncertain significance ★ ⚠ same type
PPP3CB p.Arg223Thr Uncertain significance ★ ⚠ same type
PPP3CB p.Arg82Gln Uncertain significance ★ ⚠ same type
PPP3CB p.Asn489His Uncertain significance ★ ⚠ same type
PPP3CB p.Asp47Val Uncertain significance ★ ⚠ 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/ppp3cb-p-val52ile (accessed [today's date]).

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