Is PPP2R5D p.Pro201Arg (c.602C>G) pathogenic?

PPP2R5D p.Pro201Arg (c.602C>G) is classified Pathogenic in PPP2R5D (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-21). AlphaMissense: likely pathogenic (0.999); Absent from gnomAD v4.1; Associated with Houge-Janssens syndrome 1.

What condition is associated with PPP2R5D p.Pro201Arg (c.602C>G)?

PPP2R5D p.Pro201Arg (c.602C>G) is associated with Houge-Janssens syndrome 1 (ClinVar).

How common is PPP2R5D p.Pro201Arg (c.602C>G) in the general population?

PPP2R5D p.Pro201Arg (c.602C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPP2R5D p.Pro201Arg (c.602C>G)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

PPP2R5D p.Pro201Arg

c.602C>G · rs876657383 · VCV190287

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Houge-Janssens syndrome 1

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic ✓ concordant with ClinVar · top 9% in PPP2R5D
REVEL	0.606	indeterminate
SaProt	LLR -17.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 3,668 bp · p 1.4e-28 · regional, not allelic
Overall
CADD	31.0	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: PPP2R5D
Protein: p.Pro201Arg
Coding: c.602C>G
MANE Select: NM_006245
dbSNP: rs876657383
Type: single nucleotide variant
Location: chr6:43007275 (GRCh38)
Gene constraint: LOEUF 0.234 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.69 · 2 PDB
Residue 201: a UniProt-annotated variant site (in hjs1; likely pathogenic; decreases binding to subunit ppp2ca; decreases binding to subunit ppp2r1a); an α-helix

Full PPP2R5D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Houge-Janssens syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPP2R5D p.Pro201Leu Uncertain significance ★ ⚠ same residue
PPP2R5D p.Pro201= Likely benign ★ same residue
PPP2R5D p.Arg253Pro Pathogenic/Likely pathogenic ★★ same condition
PPP2R5D p.Asp251Ala Pathogenic/Likely pathogenic ★★ same condition
PPP2R5D p.Asp251His Pathogenic/Likely pathogenic ★★ same condition
PPP2R5D p.Glu197Lys Pathogenic/Likely pathogenic ★★ same condition
PPP2R5D p.Glu200Lys Pathogenic/Likely pathogenic ★★ same condition
PPP2R5D p.Glu420Lys 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/ppp2r5d-p-pro201arg (accessed [today's date]).

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