Is PPP2CA p.Ala182Val (c.545C>T) pathogenic?

PPP2CA p.Ala182Val (c.545C>T) is classified Uncertain significance in PPP2CA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-31). AlphaMissense: likely benign (0.2683); Very rare (popmax 8.49e-05%, nfe).

How common is PPP2CA p.Ala182Val (c.545C>T) in the general population?

PPP2CA p.Ala182Val (c.545C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about PPP2CA p.Ala182Val (c.545C>T)?

AlphaMissense predicts likely benign (score 0.2683) — an in-silico prediction, not a clinical call.

PPP2CA p.Ala182Val

c.545C>T · rs2481049614 · VCV2748609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2683	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.14	constrained · MANE · 4,233 bp · p 7.9e-44 · regional, not allelic
Overall
CADD	26.3	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 8.49e-05% European (non-Finnish) · 1/1,178,418 alleles

Overall 6.2e-05% 1/1,612,422 alleles · very rare exomes 1/1,460,092 · genomes 0/152,330 · 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.Ala182Val
Coding: c.545C>T
MANE Select: NM_002715
dbSNP: rs2481049614
Type: single nucleotide variant
Location: chr5:134201016 (GRCh38)
Gene constraint: LOEUF 0.315 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.86 · 50 PDB
Residue 182: a UniProt-annotated variant site (in hjs3; may be expressed at very low levels, if any); an α-helix

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

Similar variants

PPP2CA p.Asp223His Pathogenic/Likely pathogenic ★★ same type
PPP2CA p.Asp88Gly Pathogenic/Likely pathogenic ★★ same type
PPP2CA p.Gln122His Likely pathogenic ★★ same type
PPP2CA p.His191Arg Pathogenic/Likely pathogenic ★★ same type
PPP2CA p.Tyr127Cys Likely pathogenic ★★ same type
PPP2CA p.Tyr265Cys Likely pathogenic ★★ same type
PPP2CA p.Arg108Cys Uncertain significance ★★ ⚠ same type
PPP2CA p.Asp57Asn Uncertain significance ★★ ⚠ 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/ppp2ca-p-ala182val (accessed [today's date]).

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