Is PPIL1 p.Gln63Pro (c.188A>C) pathogenic?

PPIL1 p.Gln63Pro (c.188A>C) is classified Uncertain significance in PPIL1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9876); Absent from gnomAD v4.1; Associated with pontocerebellar hypoplasia, type 14.

What condition is associated with PPIL1 p.Gln63Pro (c.188A>C)?

PPIL1 p.Gln63Pro (c.188A>C) is associated with pontocerebellar hypoplasia, type 14 (ClinVar).

How common is PPIL1 p.Gln63Pro (c.188A>C) in the general population?

PPIL1 p.Gln63Pro (c.188A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPIL1 p.Gln63Pro (c.188A>C)?

AlphaMissense predicts likely pathogenic (score 0.9876) — an in-silico prediction, not a clinical call.

PPIL1 p.Gln63Pro

c.188A>C · VCV3377734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9876 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pontocerebellar hypoplasia, type 14

Computational evidence

Protein change
AlphaMissense	0.9876	likely pathogenic
REVEL	0.744	pathogenic-leaning
SaProt	LLR -13.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.078 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: PPIL1
Protein: p.Gln63Pro
Coding: c.188A>C
MANE Select: NM_016059
Type: single nucleotide variant
Location: chr6:36871741 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 32 PDB
Residue 63: the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in pch14); a binding site; a β-strand

Full PPIL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia, type 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPIL1 c.280+1G>A Likely pathogenic ★ same condition
PPIL1 p.Arg45Ter Likely pathogenic ★ same condition
PPIL1 p.Ala117Asp Uncertain significance ★ ⚠ same condition
PPIL1 p.Ala117Thr Uncertain significance ★ ⚠ same condition
PPIL1 p.Asp106Asn Uncertain significance ★ ⚠ same condition
PPIL1 p.Thr115Asn Uncertain significance ★ ⚠ same condition
PPIL1 p.Thr127Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
PPIL1 p.Thr93Pro Uncertain significance ★ ⚠ 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/ppil1-p-gln63pro (accessed [today's date]).

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