Is PPM1D p.Pro88Ser (c.262C>T) pathogenic?

PPM1D p.Pro88Ser (c.262C>T) is classified Benign in PPM1D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.0664); Low-frequency (popmax 2.76%, eas).

How common is PPM1D p.Pro88Ser (c.262C>T) in the general population?

PPM1D p.Pro88Ser (c.262C>T) is low-frequency (popmax 2.76%, eas) (gnomAD).

What do computational predictors say about PPM1D p.Pro88Ser (c.262C>T)?

AlphaMissense predicts likely benign (score 0.0664) — an in-silico prediction, not a clinical call.

PPM1D p.Pro88Ser

c.262C>T · rs139928505 · VCV696660

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0664 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.76%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0664	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.65	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 -0.16	GERP -2.1
Regional constraint	o/e 0.88	unconstrained · MANE · 307 bp · p 0.13 · regional, not allelic
Overall
CADD	11.38	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 2.76% East Asian · 1,174/42,488 alleles

Filtering AF 2.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.58%

Overall 0.0788% 1,239/1,572,616 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.76%	36
Remaining individualsnot grpmax-eligible	0.064%	1,562
Ashkenazi Jewishnot grpmax-eligible	0.0463%	2,161
Middle Eastern	0.0171%	5,860
South Asian	0.0046%	21,749
European (non-Finnish)	0.000689%	145,233

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: PPM1D
Protein: p.Pro88Ser
Coding: c.262C>T
MANE Select: NM_003620
dbSNP: rs139928505
Type: single nucleotide variant
Location: chr17:60600676 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 1 PDB
Residue 88: the ppm-type phosphatase domain; the 'interaction with chek1' region; the 'disordered' region

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

Similar variants

PPM1D p.Pro88Leu Likely benign ★ same residue
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

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-pro88ser (accessed [today's date]).

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