Is PPM1D p.Ala82Ser (c.244G>T) pathogenic?

PPM1D p.Ala82Ser (c.244G>T) is classified Benign in PPM1D (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0786); Low-frequency (popmax 1.87%, afr).

How common is PPM1D p.Ala82Ser (c.244G>T) in the general population?

PPM1D p.Ala82Ser (c.244G>T) is low-frequency (popmax 1.87%, afr) (gnomAD).

What do computational predictors say about PPM1D p.Ala82Ser (c.244G>T)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

PPM1D p.Ala82Ser

c.244G>T · rs34632861 · VCV695416

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.87%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.42	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 0.32	GERP -2, phastCons 0.77
Regional constraint	o/e 0.88	unconstrained · MANE · 307 bp · p 0.13 · regional, not allelic
Overall
CADD	8.52	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 1.87% African / African-American · 1,352/72,340 alleles

Filtering AF 1.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.75%

Overall 0.0949% 1,471/1,549,630 alleles · low-frequency exomes 622/1,397,360 · genomes 849/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.87%	54
Remaining individualsnot grpmax-eligible	0.108%	923
Admixed American	0.0779%	1,283
Middle Eastern	0.0531%	1,882
Ashkenazi Jewishnot grpmax-eligible	0.00365%	27,428
South Asian	0.00119%	84,382
European (non-Finnish)	0.000868%	115,150

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.Ala82Ser
Coding: c.244G>T
MANE Select: NM_003620
dbSNP: rs34632861
Type: single nucleotide variant
Location: chr17:60600658 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 1 PDB
Residue 82: 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.Ala82= 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-ala82ser (accessed [today's date]).

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