Is PPP2CA p.Ser24Phe (c.71C>T) pathogenic?

PPP2CA p.Ser24Phe (c.71C>T) is classified Uncertain significance in PPP2CA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-24). AlphaMissense: ambiguous (0.5523); Very rare (popmax 8.48e-05%, nfe).

How common is PPP2CA p.Ser24Phe (c.71C>T) in the general population?

PPP2CA p.Ser24Phe (c.71C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PPP2CA p.Ser24Phe (c.71C>T)?

AlphaMissense predicts ambiguous (score 0.5523) — an in-silico prediction, not a clinical call.

PPP2CA p.Ser24Phe

c.71C>T · VCV3679635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5523 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

⚠ 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	0.5523	ambiguous
REVEL	0.349	indeterminate
SaProt	LLR -14.31	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 0.79, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 20 kb · p 0.0022 · regional, not allelic
Overall
CADD	27.5	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,178 alleles

Overall 6.21e-05% 1/1,610,604 alleles · very rare exomes 0/1,458,394 · genomes 1/152,210 · 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.Ser24Phe
Coding: c.71C>T
MANE Select: NM_002715
Type: single nucleotide variant
Location: chr5:134225791 (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-ser24phe (accessed [today's date]).

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