Is PPM1D p.Glu30= (c.90G>A) pathogenic?

PPM1D p.Glu30= (c.90G>A) is classified Benign in PPM1D (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with PPM1D p.Glu30= (c.90G>A)?

PPM1D p.Glu30= (c.90G>A) is associated with hereditary neoplastic syndrome (ClinVar).

PPM1D p.Glu30=

Q: How common is PPM1D p.Glu30= (c.90G>A) in the general population?

PPM1D p.Glu30= (c.90G>A) is common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.90G>A · rs16944543 · VCV1277034

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.65, phastCons 1
Overall
CADD	9.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.2% African / African-American · 11,999/74,112 alleles

Filtering AF 15.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.8%

Overall 0.88% 13,812/1,570,158 alleles · common exomes 6,701/1,417,912 · genomes 7,111/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.2%	6
Admixed American	1.37%	73
Remaining individualsnot grpmax-eligible	1.26%	80
Middle Eastern	0.501%	200
South Asian	0.0386%	2,592
East Asian	0.035%	2,854
European (non-Finnish)	0.0218%	4,577

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.Glu30=
Coding: c.90G>A
MANE Select: NM_003620
dbSNP: rs16944543
Type: single nucleotide variant
Location: chr17:60600504 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 1 PDB
Residue 30: the ppm-type phosphatase domain; the 'interaction with chek1' region; the 'disordered' region; a β-strand

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPM1D c.827-12C>A Benign ★★ same condition
PPM1D c.1017+51A>G Benign/Likely benign ★ same condition
PPM1D c.1017+3929A>C Likely benign same condition
PPM1D c.1260+2807G>A Likely benign same condition
PPM1D c.1261-1386A>G Likely benign same condition
PPM1D c.472+1152A>G Likely benign same condition
PPM1D c.472+314G>A Likely benign same condition
PPM1D c.472+4585C>T Likely benign same condition

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-glu30 (accessed [today's date]).

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