Is PPP3CA p.His92Arg (c.275A>G) pathogenic?

PPP3CA p.His92Arg (c.275A>G) is classified Pathogenic/Likely pathogenic in PPP3CA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-24). AlphaMissense: likely pathogenic (0.9975); No allele count reported in gnomAD v4.1 (AN 1,613,330); Associated with Inborn genetic diseases.

What condition is associated with PPP3CA p.His92Arg (c.275A>G)?

PPP3CA p.His92Arg (c.275A>G) is associated with Inborn genetic diseases, intellectual disability, developmental and epileptic encephalopathy 91 (ClinVar).

How common is PPP3CA p.His92Arg (c.275A>G) in the general population?

PPP3CA p.His92Arg (c.275A>G) is no allele count reported in gnomAD v4.1 (AN 1,613,330) (gnomAD).

What do computational predictors say about PPP3CA p.His92Arg (c.275A>G)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

PPP3CA p.His92Arg

c.275A>G · rs1553925558 · VCV441272

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,330)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic ✓ concordant with ClinVar
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -13.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 170 kb · p 4.9e-41 · regional, not allelic
Overall
CADD	25.5	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

No allele count reported in gnomAD v4.1 (AN 1,613,330). 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.His92Arg
Coding: c.275A>G
MANE Select: NM_000944
dbSNP: rs1553925558
Type: single nucleotide variant
Location: chr4:101109063 (GRCh38)
Gene constraint: LOEUF 0.243 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.24 · 21 PDB
Residue 92: a binding site; the 'catalytic' region; a UniProt-annotated variant site (in iecee1)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability developmental and epileptic encephalopathy 91

Similar variants

PPP3CA p.His92Asp Pathogenic ★ same residue
PPP3CA p.Ala447Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
PPP3CA p.Arg254Ser Pathogenic/Likely pathogenic ★★ same condition
PPP3CA p.Asp234Glu Pathogenic/Likely pathogenic ★★ same condition
PPP3CA p.Glu282Lys Pathogenic/Likely pathogenic ★★ same condition
PPP3CA c.860+3G>A Uncertain significance ★★ same condition
PPP3CA p.Ala83Val Uncertain significance ★★ ⚠ same condition
PPP3CA p.Arg28Gln 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-his92arg (accessed [today's date]).

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