Is PPP3CB p.Phe32Ser (c.95T>C) pathogenic?

PPP3CB p.Phe32Ser (c.95T>C) is classified Uncertain significance in PPP3CB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.7619); Ultra-rare (popmax 0.0107%, afr).

How common is PPP3CB p.Phe32Ser (c.95T>C) in the general population?

PPP3CB p.Phe32Ser (c.95T>C) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about PPP3CB p.Phe32Ser (c.95T>C)?

AlphaMissense predicts likely pathogenic (score 0.7619) — an in-silico prediction, not a clinical call.

PPP3CB p.Phe32Ser

c.95T>C · VCV4143245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7619 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7619	likely pathogenic
REVEL	0.1	moderately benign-leaning
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 17 kb · p 0.031 · regional, not allelic
Overall
CADD	25.5	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 0.0107% African / African-American · 8/74,898 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000558% 9/1,613,216 alleles · ultra-rare exomes 1/1,461,036 · genomes 8/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,362
European (non-Finnish)	8.48e-05%	1,179,608

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: PPP3CB
Protein: p.Phe32Ser
Coding: c.95T>C
MANE Select: NM_021132
Type: single nucleotide variant
Location: chr10:73479508 (GRCh38)
Gene constraint: LOEUF 0.254 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.79 · 3 PDB
Residue 32: 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-phe32ser (accessed [today's date]).

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