Is PPM1D p.Ser575fs (c.1724_1725del) pathogenic?

PPM1D p.Ser575fs (c.17241725del) is classified Uncertain significance in PPM1D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). No allele count reported in gnomAD v4.1 (AN 1,614,098).

How common is PPM1D p.Ser575fs (c.1724_1725del) in the general population?

PPM1D p.Ser575fs (c.1724_1725del) is no allele count reported in gnomAD v4.1 (AN 1,614,098) (gnomAD).

PPM1D p.Ser575fs

c.1724_1725del · VCV3336004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,098)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,098). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PPM1D
Protein: p.Ser575fs
Coding: c.1724_1725del
MANE Select: NM_003620
Type: Microsatellite
Location: chr17:60663456 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 1 PDB
Residue 575: a UniProt-annotated variant site (in jdvs); a UniProt-annotated variant site (in oc; may be associated with disease susceptibility); a UniProt-annotated variant site (in bc; may be associated with disease susceptibility; gain-of-function mutation that results in increased negative regulation of p53 expression in response to ionizing radiation exposure); a UniProt-annotated variant site (in bc; may be associated with disease susceptibility); the 'disordered' region

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

Similar variants

PPM1D p.Ser575Phe Uncertain significance ★★ ⚠ same residue
PPM1D p.Ser575_Val576insTer Uncertain significance ★ same residue
PPM1D p.Thr506fs Uncertain significance ★★ same type
PPM1D p.Pro437fs Pathogenic ★ same type
PPM1D p.Cys92_Arg93insCys Uncertain significance ★ same type
PPM1D p.His253fs Uncertain significance ★ same type
PPM1D p.Ile436fs Conflicting classifications of pathogenicity ★ same type
PPM1D p.Met409del 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-ser575fs (accessed [today's date]).

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