Is PPIL1 p.Phe82Ser (c.245T>C) pathogenic?

PPIL1 p.Phe82Ser (c.245T>C) is classified Likely pathogenic in PPIL1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-20). AlphaMissense: likely pathogenic (0.9971); Absent from gnomAD v4.1; Associated with Congenital pontocerebellar hypoplasia.

What condition is associated with PPIL1 p.Phe82Ser (c.245T>C)?

PPIL1 p.Phe82Ser (c.245T>C) is associated with Congenital pontocerebellar hypoplasia (ClinVar).

How common is PPIL1 p.Phe82Ser (c.245T>C) in the general population?

PPIL1 p.Phe82Ser (c.245T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPIL1 p.Phe82Ser (c.245T>C)?

AlphaMissense predicts likely pathogenic (score 0.9971) — an in-silico prediction, not a clinical call.

PPIL1 p.Phe82Ser

c.245T>C · rs2150653717 · VCV1344824

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9971 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Congenital pontocerebellar hypoplasia

Computational evidence

Protein change
AlphaMissense	0.9971	likely pathogenic ✓ concordant with ClinVar · top 3% in PPIL1
REVEL	0.633	indeterminate
SaProt	LLR -15.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.078 · regional, not allelic
Overall
CADD	28.2	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: PPIL1
Protein: p.Phe82Ser
Coding: c.245T>C
MANE Select: NM_016059
dbSNP: rs2150653717
Type: single nucleotide variant
Location: chr6:36856621 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 32 PDB
Residue 82: the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in pch14); a UniProt-annotated variant site (in pch14; uncertain significance; strongly reduced protein levels compared to wild-type after transfection in hek293t cell line)

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

Disease context

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

Similar variants

PPIL1 p.Ala99Thr Pathogenic/Likely pathogenic same condition
PPIL1 p.Arg131Gln Likely pathogenic ⚠ same condition
PPIL1 p.Gly109Cys Likely pathogenic same condition
PPIL1 p.Thr107Ala Pathogenic/Likely pathogenic same condition
PPIL1 p.Tyr78Cys Likely pathogenic same condition
PPIL1 p.Ala101_Asp106dup Likely pathogenic same condition
PPIL1 c.280+1G>A Likely pathogenic ★ same type
PPIL1 p.Arg45Ter Likely pathogenic ★ 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/ppil1-p-phe82ser (accessed [today's date]).

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