Is PPIB p.Arg51Ter (c.151C>T) pathogenic?

PPIB p.Arg51Ter (c.151C>T) is classified Pathogenic in PPIB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-26). Very rare (popmax 0.000678%, nfe).

How common is PPIB p.Arg51Ter (c.151C>T) in the general population?

PPIB p.Arg51Ter (c.151C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

PPIB p.Arg51Ter

c.151C>T · VCV3612403

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

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 5
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP -1.4, phastCons 0.88
Overall
CADD	39.0	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 0.000678% European (non-Finnish) · 8/1,179,192 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,214 alleles · very rare exomes 8/1,460,946 · genomes 0/152,268 · joint denominator

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: PPIB
Protein: p.Arg51Ter
Coding: c.151C>T
MANE Select: NM_000942
Type: single nucleotide variant
Location: chr15:64162139 (GRCh38)
Gene constraint: LOEUF 1.104 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.98 · 8 PDB
Residue 51: a β-strand; the ppiase cyclophilin-type domain

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

Similar variants

PPIB p.Arg51Leu Uncertain significance ★ ⚠ same residue
PPIB c.344-1G>T Pathogenic/Likely pathogenic ★★ same type
PPIB c.-91A>C Uncertain significance ★★ same type
PPIB p.Ala15Thr Uncertain significance ★★ ⚠ same type
PPIB p.Arg7Ser Uncertain significance ★★ ⚠ same type
PPIB p.Asn75Ser Uncertain significance ★★ ⚠ same type
PPIB p.Glu183Ala Uncertain significance ★★ ⚠ same type
PPIB p.Gly39Trp 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/ppib-p-arg51ter (accessed [today's date]).

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