Is PPP2CA p.Phe164fs (c.491del) pathogenic?

PPP2CA p.Phe164fs (c.491del) is classified Likely pathogenic in PPP2CA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). No gnomAD frequency available for this variant; Associated with Houge-Janssens syndrome 3.

What condition is associated with PPP2CA p.Phe164fs (c.491del)?

PPP2CA p.Phe164fs (c.491del) is associated with Houge-Janssens syndrome 3 (ClinVar).

How common is PPP2CA p.Phe164fs (c.491del) in the general population?

PPP2CA p.Phe164fs (c.491del) is no gnomAD frequency available for this variant (gnomAD).

PPP2CA p.Phe164fs

c.491del · rs2481049691 · VCV1710068

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Houge-Janssens syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP -1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PPP2CA
Protein: p.Phe164fs
Coding: c.491del
MANE Select: NM_002715
dbSNP: rs2481049691
Type: Deletion
Location: chr5:134201070 (GRCh38)
Gene constraint: LOEUF 0.315 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.86 · 50 PDB
Residue 164: a UniProt-annotated variant site (in hjs3; may be expressed at very low levels, if any); a β-strand

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

Disease context

Houge-Janssens syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPP2CA p.Tyr127fs Pathogenic ★ same condition
PPP2CA p.Phe164= Likely benign ★ same residue
PPP2CA p.Phe146fs Pathogenic same condition
PPP2CA p.Asp223His Pathogenic/Likely pathogenic ★★ same condition
PPP2CA p.Asp88Gly Pathogenic/Likely pathogenic ★★ same condition
PPP2CA p.Gln122His Likely pathogenic ★★ same condition
PPP2CA p.His191Arg Pathogenic/Likely pathogenic ★★ same condition
PPP2CA p.Tyr127Cys Likely 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/ppp2ca-p-phe164fs (accessed [today's date]).

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