Is PPP2CA p.Asp290Glu (c.870C>G) pathogenic?

PPP2CA p.Asp290Glu (c.870C>G) is classified Uncertain significance in PPP2CA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). AlphaMissense: likely pathogenic (0.6766); Absent from gnomAD v4.1.

How common is PPP2CA p.Asp290Glu (c.870C>G) in the general population?

PPP2CA p.Asp290Glu (c.870C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPP2CA p.Asp290Glu (c.870C>G)?

AlphaMissense predicts likely pathogenic (score 0.6766) — an in-silico prediction, not a clinical call.

PPP2CA p.Asp290Glu

c.870C>G · VCV3608525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6766 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6766	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP -2.2, phastCons 1
Regional constraint	o/e 0.14	constrained · MANE · 4,233 bp · p 7.9e-44 · regional, not allelic
Overall
CADD	17.17	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: PPP2CA
Protein: p.Asp290Glu
Coding: c.870C>G
MANE Select: NM_002715
Type: single nucleotide variant
Location: chr5:134197832 (GRCh38)
Gene constraint: LOEUF 0.315 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.86 · 50 PDB
Residue 290: a UniProt-annotated variant site (in hjs3; may be expressed at very low levels, if any); a UniProt-annotated variant site (in hjs3; loss of phosphatase activity in an in vitro assay; complete loss of interaction with pp2a subunit a ppp2r1a/ppp2r1b; interacts with alpha4/igbp1; loss of interaction with pp2a subunit b components); an α-helix

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-asp290glu (accessed [today's date]).

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