Is PPIL1 p.Arg45Ter (c.133C>T) pathogenic?

PPIL1 p.Arg45Ter (c.133C>T) is classified Likely pathogenic in PPIL1 (ClinVar, Single submitter, 3 submitters; last evaluated 2019-05-02). Very rare (popmax 0.00168%, amr); Associated with neurodevelopmental disorder.

What condition is associated with PPIL1 p.Arg45Ter (c.133C>T)?

PPIL1 p.Arg45Ter (c.133C>T) is associated with neurodevelopmental disorder, pontocerebellar hypoplasia, type 14 (ClinVar).

How common is PPIL1 p.Arg45Ter (c.133C>T) in the general population?

PPIL1 p.Arg45Ter (c.133C>T) is very rare (popmax 0.00168%, amr) (gnomAD).

PPIL1 p.Arg45Ter

c.133C>T · rs1774516234 · VCV929944

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.8, phastCons 1
Overall
CADD	51.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,580 alleles

Overall 0.000186% 3/1,611,426 alleles · very rare exomes 2/1,459,322 · genomes 1/152,104 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,580
South Asian	0.00111%	90,456
European (non-Finnish)	8.48e-05%	1,179,030

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: PPIL1
Protein: p.Arg45Ter
Coding: c.133C>T
MANE Select: NM_016059
dbSNP: rs1774516234
Type: single nucleotide variant
Location: chr6:36871796 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 32 PDB
Residue 45: the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in pch14); an α-helix

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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pontocerebellar hypoplasia, type 14

Similar variants

PPIL1 c.280+1G>A 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.Gln63Pro 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-arg45ter (accessed [today's date]).

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