Is PPP3CA p.Ile230Thr (c.689T>C) pathogenic?

PPP3CA p.Ile230Thr (c.689T>C) is classified Uncertain significance in PPP3CA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely pathogenic (0.925); Absent from gnomAD v4.1.

How common is PPP3CA p.Ile230Thr (c.689T>C) in the general population?

PPP3CA p.Ile230Thr (c.689T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPP3CA p.Ile230Thr (c.689T>C)?

AlphaMissense predicts likely pathogenic (score 0.925) — an in-silico prediction, not a clinical call.

PPP3CA p.Ile230Thr

c.689T>C · rs2475915871 · VCV2998843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.925 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.925	likely pathogenic
REVEL	0.363	indeterminate
SaProt	LLR -10.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, 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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPP3CA
Protein: p.Ile230Thr
Coding: c.689T>C
MANE Select: NM_000944
dbSNP: rs2475915871
Type: single nucleotide variant
Location: chr4:101093869 (GRCh38)
Gene constraint: LOEUF 0.243 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.24 · 21 PDB
Residue 230: the 'catalytic' region; an α-helix

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

Similar variants

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
PPP3CA c.1081+4T>A 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/ppp3ca-p-ile230thr (accessed [today's date]).

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