Is PPME1 p.Pro45Ser (c.133C>T) pathogenic?

PPME1 p.Pro45Ser (c.133C>T) is classified Likely benign in PPME1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0725); Absent from gnomAD v4.1.

How common is PPME1 p.Pro45Ser (c.133C>T) in the general population?

PPME1 p.Pro45Ser (c.133C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPME1 p.Pro45Ser (c.133C>T)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

PPME1 p.Pro45Ser

c.133C>T · VCV4142703

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -4.16	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 0.18	GERP -1.6, phastCons 0.96
Regional constraint	o/e 0.92	unconstrained · MANE · 59 kb · p 0.3 · regional, not allelic
Overall
CADD	11.64	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPME1
Protein: p.Pro45Ser
Coding: c.133C>T
MANE Select: NM_016147
Type: single nucleotide variant
Location: chr11:74203759 (GRCh38)
Gene constraint: LOEUF 0.451 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.13 · 3 PDB
Residue 45: an α-helix

Full PPME1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPME1 p.Ala98Glu Uncertain significance ★ ⚠ same type
PPME1 p.Arg12Leu Uncertain significance ★ ⚠ same type
PPME1 p.Arg16Leu Uncertain significance ★ ⚠ same type
PPME1 p.Arg199Trp Uncertain significance ★ ⚠ same type
PPME1 p.Arg228Cys Uncertain significance ★ ⚠ same type
PPME1 p.Arg32Gly Uncertain significance ★ ⚠ same type
PPME1 p.Arg39Gln Uncertain significance ★ ⚠ same type
PPME1 p.Arg68Gln 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/ppme1-p-pro45ser (accessed [today's date]).

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