Is PPIL1 p.Pro5= (c.15C>A) pathogenic?

PPIL1 p.Pro5= (c.15C>A) is classified Likely benign in PPIL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). Ultra-rare (popmax 0.099%, mid).

How common is PPIL1 p.Pro5= (c.15C>A) in the general population?

PPIL1 p.Pro5= (c.15C>A) is ultra-rare (popmax 0.099%, mid) (gnomAD).

PPIL1 p.Pro5=

c.15C>A · rs147328340 · VCV3024893

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.17	GERP -0.37, phastCons 0.87
Overall
CADD	11.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,060 alleles

Filtering AF 0.0703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0646%

Overall 0.0354% 571/1,614,136 alleles · ultra-rare exomes 541/1,461,776 · genomes 30/152,360 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
South Asian	0.0856%	1,168
Remaining individualsnot grpmax-eligible	0.056%	1,785
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
European (non-Finnish)	0.0367%	2,725
Admixed American	0.00333%	30,016
East Asian	0.00223%	44,890
African / African-American	0.00133%	75,062

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.Pro5=
Coding: c.15C>A
MANE Select: NM_016059
dbSNP: rs147328340
Type: single nucleotide variant
Location: chr6:36874758 (GRCh38)

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

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-pro5 (accessed [today's date]).

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