Is PPIB p.Asn8= (c.24C>T) pathogenic?

PPIB p.Asn8= (c.24C>T) is classified Likely benign in PPIB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-02). Ultra-rare (popmax 0.0352%, sas).

How common is PPIB p.Asn8= (c.24C>T) in the general population?

PPIB p.Asn8= (c.24C>T) is ultra-rare (popmax 0.0352%, sas) (gnomAD).

PPIB p.Asn8=

c.24C>T · rs148644836 · VCV1672923

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0352%, sas)

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 0.098	GERP -0.47, phastCons 0.7
Overall
CADD	8.957	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0352% South Asian · 32/90,976 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0223%

Overall 0.00341% 55/1,613,446 alleles · ultra-rare exomes 43/1,461,134 · genomes 12/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0352%	2,843
African / African-American	0.028%	3,573
Admixed American	0.00167%	60,010
European (non-Finnish)	8.48e-05%	1,179,816

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.Asn8=
Coding: c.24C>T
MANE Select: NM_000942
dbSNP: rs148644836
Type: single nucleotide variant
Location: chr15:64162963 (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.Asn8Ser 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-asn8 (accessed [today's date]).

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