Is PPP2CA p.Glu47= (c.141G>A) pathogenic?

PPP2CA p.Glu47= (c.141G>A) is classified Likely benign in PPP2CA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). Very rare (popmax 8.47e-05%, nfe).

How common is PPP2CA p.Glu47= (c.141G>A) in the general population?

PPP2CA p.Glu47= (c.141G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PPP2CA p.Glu47=

c.141G>A · VCV3691294

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -2.5, phastCons 0.29
Overall
CADD	16.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 0.000124% 2/1,614,010 alleles · very rare exomes 1/1,461,798 · genomes 1/152,212 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)grpmax	8.47e-05%	1,180,013

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PPP2CA
Protein: p.Glu47=
Coding: c.141G>A
MANE Select: NM_002715
Type: single nucleotide variant
Location: chr5:134206093 (GRCh38)
Gene constraint: LOEUF 0.315 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.86 · 50 PDB
Residue 47: a β-strand

Full PPP2CA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPP2CA p.Asp223His Pathogenic/Likely pathogenic ★★ same type
PPP2CA p.Asp88Gly Pathogenic/Likely pathogenic ★★ same type
PPP2CA p.Gln122His Likely pathogenic ★★ same type
PPP2CA p.His191Arg Pathogenic/Likely pathogenic ★★ same type
PPP2CA p.Tyr127Cys Likely pathogenic ★★ same type
PPP2CA p.Tyr265Cys Likely pathogenic ★★ same type
PPP2CA p.Arg108Cys Uncertain significance ★★ ⚠ same type
PPP2CA p.Asp57Asn 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/ppp2ca-p-glu47 (accessed [today's date]).

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