Is PPIL1 p.Asp156= (c.468C>T) pathogenic?

PPIL1 p.Asp156= (c.468C>T) is classified Likely benign in PPIL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-01). Ultra-rare (popmax 0.0579%, eas).

How common is PPIL1 p.Asp156= (c.468C>T) in the general population?

PPIL1 p.Asp156= (c.468C>T) is ultra-rare (popmax 0.0579%, eas) (gnomAD).

PPIL1 p.Asp156=

c.468C>T · VCV3388650

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0579%, eas)

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 -2.4	GERP -5.6
Overall
CADD	2.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0579% East Asian · 26/44,878 alleles

Filtering AF 0.0417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0374%

Overall 0.0281% 454/1,614,148 alleles · ultra-rare exomes 421/1,461,894 · genomes 33/152,254 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0579%	1,726
South Asian	0.0538%	1,859
Remaining individualsnot grpmax-eligible	0.0336%	2,976
European (non-Finnish)	0.0288%	3,471
Admixed American	0.0233%	4,287
African / African-American	0.00533%	18,757

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: PPIL1
Protein: p.Asp156=
Coding: c.468C>T
MANE Select: NM_016059
Type: single nucleotide variant
Location: chr6:36855846 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06 · 32 PDB
Residue 156: the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in pch14)

Full PPIL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPIL1 c.280+1G>A Likely pathogenic ★ same type
PPIL1 p.Arg45Ter Likely pathogenic ★ same type
PPIL1 p.Ala117Asp Uncertain significance ★ ⚠ same type
PPIL1 p.Ala117Thr Uncertain significance ★ ⚠ same type
PPIL1 p.Arg141Cys Uncertain significance ★ ⚠ same type
PPIL1 p.Arg44Cys Uncertain significance ★ ⚠ same type
PPIL1 p.Arg44Leu Uncertain significance ★ ⚠ same type
PPIL1 p.Asn102Ile 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/ppil1-p-asp156 (accessed [today's date]).

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