Is PPIB p.Met9Arg (c.26T>G) pathogenic?

PPIB p.Met9Arg (c.26T>G) is classified Uncertain significance in PPIB (ClinVar, Single submitter, 3 submitters; last evaluated 2024-03-26). AlphaMissense: likely benign (0.1304); Absent from gnomAD v4.1; Associated with osteogenesis imperfecta type 9.

What condition is associated with PPIB p.Met9Arg (c.26T>G)?

PPIB p.Met9Arg (c.26T>G) is associated with osteogenesis imperfecta type 9 (ClinVar).

How common is PPIB p.Met9Arg (c.26T>G) in the general population?

PPIB p.Met9Arg (c.26T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPIB p.Met9Arg (c.26T>G)?

AlphaMissense predicts likely benign (score 0.1304) — an in-silico prediction, not a clinical call.

PPIB p.Met9Arg

c.26T>G · rs137853864 · VCV16927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1304 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

osteogenesis imperfecta type 9

Computational evidence

Protein change
AlphaMissense	0.1304	likely benign
REVEL	0.487	indeterminate
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,960 bp · p 0.77 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPIB
Protein: p.Met9Arg
Coding: c.26T>G
MANE Select: NM_000942
dbSNP: rs137853864
Type: single nucleotide variant
Location: chr15:64162961 (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 9: a UniProt-annotated variant site (in oi9; patients have white sclerae, normal dentition, no rhizomelia or severe deformity of long bones)

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.Met9Val Likely pathogenic ★ ⚠ same residue
PPIB p.Met9Lys Likely pathogenic ★ ⚠ 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

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-met9arg (accessed [today's date]).

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