Is PPM1D p.Ala102Ser (c.304G>T) pathogenic?

PPM1D p.Ala102Ser (c.304G>T) is classified Uncertain significance in PPM1D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: ambiguous (0.4208); Very rare (popmax 0.0017%, amr).

How common is PPM1D p.Ala102Ser (c.304G>T) in the general population?

PPM1D p.Ala102Ser (c.304G>T) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about PPM1D p.Ala102Ser (c.304G>T)?

AlphaMissense predicts ambiguous (score 0.4208) — an in-silico prediction, not a clinical call.

PPM1D p.Ala102Ser

c.304G>T · VCV3606704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4208 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Computational evidence

Protein change
AlphaMissense	0.4208	ambiguous
REVEL	0.369	indeterminate
SaProt	LLR -7.48	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 307 bp · p 0.13 · regional, not allelic
Overall
CADD	33.0	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 0.0017% Admixed American · 1/58,966 alleles

Overall 6.87e-05% 1/1,455,498 alleles · very rare

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.Ala102Ser
Coding: c.304G>T
MANE Select: NM_003620
Type: single nucleotide variant
Location: chr17:60600718 (GRCh38)
Gene constraint: LOEUF 1.183 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 68.15 · 1 PDB
Residue 102: the ppm-type phosphatase domain; a β-strand

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

Similar variants

PPM1D p.Ala102Thr Uncertain significance ★ ⚠ 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-ala102ser (accessed [today's date]).

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