Is PPP2CA p.Val28Ile (c.82G>A) pathogenic?

PPP2CA p.Val28Ile (c.82G>A) is classified Uncertain significance in PPP2CA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-19). AlphaMissense: likely benign (0.1661); Very rare (popmax 0.00017%, nfe).

How common is PPP2CA p.Val28Ile (c.82G>A) in the general population?

PPP2CA p.Val28Ile (c.82G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about PPP2CA p.Val28Ile (c.82G>A)?

AlphaMissense predicts likely benign (score 0.1661) — an in-silico prediction, not a clinical call.

PPP2CA p.Val28Ile

c.82G>A · VCV4972072

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1661 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1661	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 20 kb · p 0.0022 · regional, not allelic
Overall
CADD	23.1	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,798 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,609,372 alleles · very rare exomes 2/1,457,060 · genomes 0/152,312 · joint denominator

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: PPP2CA
Protein: p.Val28Ile
Coding: c.82G>A
MANE Select: NM_002715
Type: single nucleotide variant
Location: chr5:134225780 (GRCh38)

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

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-val28ile (accessed [today's date]).

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