Is PPIB p.Arg7Ser (c.19C>A) pathogenic?

PPIB p.Arg7Ser (c.19C>A) is classified Uncertain significance in PPIB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-06). AlphaMissense: ambiguous (0.3869); Very rare (popmax 0.00229%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PPIB p.Arg7Ser (c.19C>A)?

PPIB p.Arg7Ser (c.19C>A) is associated with Inborn genetic diseases (ClinVar).

How common is PPIB p.Arg7Ser (c.19C>A) in the general population?

PPIB p.Arg7Ser (c.19C>A) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about PPIB p.Arg7Ser (c.19C>A)?

AlphaMissense predicts ambiguous (score 0.3869) — an in-silico prediction, not a clinical call.

PPIB p.Arg7Ser

c.19C>A · rs760906683 · VCV2354586

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3869 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3869	ambiguous
REVEL	0.229	benign-leaning
SaProt	LLR -6.68	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,960 bp · p 0.77 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,179,750 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00167% 27/1,613,110 alleles · very rare

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.Arg7Ser
Coding: c.19C>A
MANE Select: NM_000942
dbSNP: rs760906683
Type: single nucleotide variant
Location: chr15:64162968 (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

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

Similar variants

PPIB p.Arg7Cys Uncertain significance ★ same residue
PPIB p.Asn75Ser Uncertain significance ★★ ⚠ same condition
PPIB p.Glu183Ala Uncertain significance ★★ ⚠ same condition
PPIB p.Gly39Trp Uncertain significance ★★ ⚠ same condition
PPIB p.Lys116Arg 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

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-arg7ser (accessed [today's date]).

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