Is PPM1F p.Pro6Leu (c.17C>T) pathogenic?

PPM1F p.Pro6Leu (c.17C>T) is classified Uncertain significance in PPM1F (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.0864); Absent from gnomAD v4.1.

How common is PPM1F p.Pro6Leu (c.17C>T) in the general population?

PPM1F p.Pro6Leu (c.17C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPM1F p.Pro6Leu (c.17C>T)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

PPM1F p.Pro6Leu

c.17C>T · rs2517595672 · VCV2485948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.74	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 1	GERP -0.73, phastCons 0.23
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 0.031 · regional, not allelic
Overall
CADD	19.91	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: PPM1F
Protein: p.Pro6Leu
Coding: c.17C>T
MANE Select: NM_014634
dbSNP: rs2517595672
Type: single nucleotide variant
Location: chr22:21946032 (GRCh38)
Gene constraint: LOEUF 0.864 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.70
Residue 6: the 'disordered' region

Full PPM1F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPM1F p.Arg149Gln Uncertain significance ★★ ⚠ same type
PPM1F p.Glu103Lys Uncertain significance ★★ ⚠ same type
PPM1F p.Glu82Lys Uncertain significance ★★ ⚠ same type
PPM1F p.Gly320Arg Uncertain significance ★★ ⚠ same type
PPM1F p.Gly386Glu Uncertain significance ★★ ⚠ same type
PPM1F p.His378Tyr Uncertain significance ★★ ⚠ same type
PPM1F p.Met63Val Uncertain significance ★★ ⚠ same type
PPM1F p.Pro430Leu 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/ppm1f-p-pro6leu (accessed [today's date]).

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