Is PPIB p.Arg3= (c.9C>T) pathogenic?

PPIB p.Arg3= (c.9C>T) is classified Benign/Likely benign in PPIB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Ultra-rare (popmax 0.0342%, mid).

How common is PPIB p.Arg3= (c.9C>T) in the general population?

PPIB p.Arg3= (c.9C>T) is ultra-rare (popmax 0.0342%, mid) (gnomAD).

PPIB p.Arg3=

c.9C>T · rs141504929 · VCV762447

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, mid)

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 1.9	GERP -1.7, phastCons 0.98
Overall
CADD	12.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0342% Middle Eastern · 2/5,850 alleles

Filtering AF 0.0109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0102%

Overall 0.0265% 428/1,613,176 alleles · ultra-rare exomes 361/1,460,856 · genomes 67/152,320 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.359%	279
Ashkenazi Jewishnot grpmax-eligible	0.0541%	1,849
Remaining individualsnot grpmax-eligible	0.0401%	2,497
Middle Easterngrpmax	0.0342%	2,925
European (non-Finnish)	0.0125%	7,972
South Asian	0.0066%	15,155
Admixed American	0.00333%	29,999

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg3=
Coding: c.9C>T
MANE Select: NM_000942
dbSNP: rs141504929
Type: single nucleotide variant
Location: chr15:64162978 (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

Similar variants

PPIB p.Arg3Pro Uncertain significance ★ ⚠ same residue
PPIB c.344-1G>T Pathogenic/Likely pathogenic ★★ same type
PPIB c.-91A>C Uncertain significance ★★ same type
PPIB p.Ala15Thr Uncertain significance ★★ ⚠ same type
PPIB p.Arg7Ser Uncertain significance ★★ ⚠ same type
PPIB p.Asn75Ser Uncertain significance ★★ ⚠ same type
PPIB p.Glu183Ala Uncertain significance ★★ ⚠ same type
PPIB p.Gly39Trp Uncertain significance ★★ ⚠ same type

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-arg3 (accessed [today's date]).

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