PPP3CA p.Arg154=
c.462A>G · rs2110254760 · VCV1539290
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00172%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 0.36, phastCons 1 |
| Overall | ||
| CADD | 9.192 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00172%
Admixed American · 1/58,096 alleles
Filtering AF
0.000362%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000262%
Overall
0.00069%
11/1,594,864 alleles · very rare
exomes 11/1,442,680 · genomes 0/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00172% | 58,096 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,656 |
| European (non-Finnish) | 0.00077% | 129,939 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- PPP3CA
- Protein
- p.Arg154=
- Coding
- c.462A>G
- MANE Select
- NM_000944
- dbSNP
- rs2110254760
- Type
- single nucleotide variant
- Location
- chr4:101099645 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 21 PDB
- Residue 154
- the 'catalytic' region; an α-helix
Similar variants
- PPP3CA p.Arg154Gly Uncertain significance ★ ⚠ same residue
- PPP3CA c.1340-2A>G Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Ala447Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPP3CA p.Arg254Ser Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Asp234Glu Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Glu282Lys Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Glu456Ter Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.His92Arg Pathogenic/Likely pathogenic ★★ 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/ppp3ca-p-arg154 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown