Is PPIB p.Phe93= (c.279C>T) pathogenic?

PPIB p.Phe93= (c.279C>T) is classified Uncertain significance in PPIB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00439%, sas); Associated with osteogenesis imperfecta type 9.

What condition is associated with PPIB p.Phe93= (c.279C>T)?

PPIB p.Phe93= (c.279C>T) is associated with osteogenesis imperfecta type 9 (ClinVar).

How common is PPIB p.Phe93= (c.279C>T) in the general population?

PPIB p.Phe93= (c.279C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

PPIB p.Phe93=

c.279C>T · rs886051323 · VCV316704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

osteogenesis imperfecta type 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.1, phastCons 1
Overall
CADD	12.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,078 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,614,096 alleles · very rare exomes 4/1,461,818 · genomes 0/152,278 · 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.Phe93=
Coding: c.279C>T
MANE Select: NM_000942
dbSNP: rs886051323
Type: single nucleotide variant
Location: chr15:64160168 (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 93: the ppiase cyclophilin-type domain

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

Disease context

osteogenesis imperfecta type 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPIB c.-91A>C Uncertain significance ★★ same condition
PPIB p.Asn75Ser Uncertain significance ★★ ⚠ same condition
PPIB p.Phe100Leu Uncertain significance ★★ ⚠ same condition
PPIB c.135+14C>T Likely benign ★★ same condition
PPIB c.249+19G>T Benign/Likely benign ★★ same condition
PPIB c.529-21G>A Benign ★★ same condition
PPIB p.Gly29Arg Benign/Likely benign ★★ same condition
PPIB p.Ile205= Likely benign ★★ 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/ppib-p-phe93 (accessed [today's date]).

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