Is PPM1D p.Pro33Ser (c.97C>T) pathogenic?

PPM1D p.Pro33Ser (c.97C>T) is classified Uncertain significance in PPM1D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely benign (0.0977); Absent from gnomAD v4.1.

How common is PPM1D p.Pro33Ser (c.97C>T) in the general population?

PPM1D p.Pro33Ser (c.97C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPM1D p.Pro33Ser (c.97C>T)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

PPM1D p.Pro33Ser

c.97C>T · VCV3726260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.48, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 307 bp · p 0.13 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: PPM1D
Protein: p.Pro33Ser
Coding: c.97C>T
MANE Select: NM_003620
Type: single nucleotide variant
Location: chr17:60600511 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 1 PDB
Residue 33: the ppm-type phosphatase domain; the 'interaction with chek1' region; the 'disordered' region; a turn

Full PPM1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPM1D p.Cys407Ter Pathogenic/Likely pathogenic ★★ same type
PPM1D p.Gln404Ter Pathogenic ★★ same type
PPM1D p.Gln462Ter Likely pathogenic ★★ same type
PPM1D p.Glu423Ter Pathogenic ★★ same type
PPM1D p.Ser421Ter Pathogenic/Likely pathogenic ★★ same type
PPM1D p.Trp427Ter Pathogenic ★★ same type
PPM1D p.Arg357Cys Uncertain significance ★★ ⚠ same type
PPM1D p.Arg557Ter 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/ppm1d-p-pro33ser (accessed [today's date]).

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