Is PPIB p.Ala19= (c.57G>T) pathogenic?

PPIB p.Ala19= (c.57G>T) is classified Uncertain significance in PPIB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). No allele count reported in gnomAD v4.1 (AN 1,613,542); Associated with osteogenesis imperfecta type 9.

What condition is associated with PPIB p.Ala19= (c.57G>T)?

PPIB p.Ala19= (c.57G>T) is associated with osteogenesis imperfecta type 9 (ClinVar).

How common is PPIB p.Ala19= (c.57G>T) in the general population?

PPIB p.Ala19= (c.57G>T) is no allele count reported in gnomAD v4.1 (AN 1,613,542) (gnomAD).

PPIB p.Ala19=

c.57G>T · rs2081570846 · VCV888473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,542)

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 3.1	GERP 1.7, phastCons 1
Overall
CADD	14.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,542). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PPIB
Protein: p.Ala19=
Coding: c.57G>T
MANE Select: NM_000942
dbSNP: rs2081570846
Type: single nucleotide variant
Location: chr15:64162930 (GRCh38)
Gene constraint: LOEUF 1.104 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.98 · 8 PDB

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 p.Ala19Val Likely benign ★ same residue
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

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-ala19 (accessed [today's date]).

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