Is PPP3CA p.Ser438fs (c.1308_1312dup) pathogenic?

PPP3CA p.Ser438fs (c.13081312dup) is classified Pathogenic/Likely pathogenic in PPP3CA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-16). No gnomAD frequency available for this variant; Associated with PPP3CA-related disorder.

What condition is associated with PPP3CA p.Ser438fs (c.1308_1312dup)?

PPP3CA p.Ser438fs (c.1308_1312dup) is associated with PPP3CA-related disorder, developmental and epileptic encephalopathy 91 (ClinVar).

How common is PPP3CA p.Ser438fs (c.1308_1312dup) in the general population?

PPP3CA p.Ser438fs (c.1308_1312dup) is no gnomAD frequency available for this variant (gnomAD).

PPP3CA p.Ser438fs

c.1308_1312dup · rs2476210016 · VCV3236340

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

PPP3CA-related disorder

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 12 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.8, 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: PPP3CA
Protein: p.Ser438fs
Coding: c.1308_1312dup
MANE Select: NM_000944
dbSNP: rs2476210016
Type: Duplication
Location: chr4:101032293 (GRCh38)
Gene constraint: LOEUF 0.243 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.24 · 21 PDB

Full PPP3CA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PPP3CA-related disorder

Also linked: developmental and epileptic encephalopathy 91

Similar variants

PPP3CA p.Thr429fs Pathogenic/Likely pathogenic ★★ same condition
PPP3CA p.Ala447fs Pathogenic ★ same condition
PPP3CA p.Gly430fs Pathogenic ★ same condition
PPP3CA p.Ser434fs Pathogenic ★ same condition
PPP3CA p.Ser446fs Pathogenic ★ same condition
PPP3CA p.Thr468fs Likely pathogenic ★ same condition
PPP3CA p.Val420fs Pathogenic ★ same condition
PPP3CA p.Glu416_Ser417insGlu Uncertain significance ★ 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/ppp3ca-p-ser438fs (accessed [today's date]).

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