Is PPIB p.Lys116Arg (c.347A>G) pathogenic?

PPIB p.Lys116Arg (c.347A>G) is classified Uncertain significance in PPIB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). AlphaMissense: likely benign (0.0989); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PPIB p.Lys116Arg (c.347A>G)?

PPIB p.Lys116Arg (c.347A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PPIB p.Lys116Arg (c.347A>G) in the general population?

PPIB p.Lys116Arg (c.347A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPIB p.Lys116Arg (c.347A>G)?

AlphaMissense predicts likely benign (score 0.0989) — an in-silico prediction, not a clinical call.

PPIB p.Lys116Arg

c.347A>G · rs2081537322 · VCV2119547

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0989 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0989	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.33	acceptor gain, 1 bp away · masked 0 · deltas
Pangolin	Δ0.26	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 0.18, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,960 bp · p 0.77 · regional, not allelic
Overall
CADD	24.3	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.Lys116Arg
Coding: c.347A>G
MANE Select: NM_000942
dbSNP: rs2081537322
Type: single nucleotide variant
Location: chr15:64156906 (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 116: the ppiase cyclophilin-type domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPIB p.Arg7Ser Uncertain significance ★★ ⚠ same condition
PPIB p.Asn75Ser Uncertain significance ★★ ⚠ same condition
PPIB p.Glu183Ala Uncertain significance ★★ ⚠ same condition
PPIB p.Gly39Trp Uncertain significance ★★ ⚠ same condition
PPIB p.Lys45Arg Uncertain significance ★★ ⚠ same condition
PPIB p.Lys92Arg Uncertain significance ★★ ⚠ same condition
PPIB p.Thr113Ile Uncertain significance ★★ ⚠ same condition
PPIB p.Tyr88Cys Uncertain significance ★★ ⚠ 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-lys116arg (accessed [today's date]).

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