Is PPIB p.Asn148= (c.444C>T) pathogenic?

PPIB p.Asn148= (c.444C>T) is classified Conflicting classifications of pathogenicity in PPIB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-12). Ultra-rare (popmax 0.0231%, sas); Associated with osteogenesis imperfecta type 9.

What condition is associated with PPIB p.Asn148= (c.444C>T)?

PPIB p.Asn148= (c.444C>T) is associated with osteogenesis imperfecta type 9 (ClinVar).

How common is PPIB p.Asn148= (c.444C>T) in the general population?

PPIB p.Asn148= (c.444C>T) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

PPIB p.Asn148=

c.444C>T · rs549542551 · VCV886217

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, 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 looked up on this page · why
Constraint at this position
Conservation	phyloP -3.3	GERP -4.5
Overall
CADD	9.495	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% South Asian · 21/91,080 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00192% 31/1,614,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,337
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
Remaining individualsnot grpmax-eligible	0.0032%	31,254
African / African-American	0.00133%	75,048
European (non-Finnish)	0.000424%	236,007

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.Asn148=
Coding: c.444C>T
MANE Select: NM_024798 · reported on NM_000942
dbSNP: rs549542551
Type: single nucleotide variant
Location: chr15:64156809 (GRCh38)

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

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-asn148 (accessed [today's date]).

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