Is PRSS1 p.Glu75= (c.225G>A) pathogenic?

PRSS1 p.Glu75= (c.225G>A) is classified Likely benign in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-23). Very rare (popmax 0.00223%, eas); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Glu75= (c.225G>A)?

PRSS1 p.Glu75= (c.225G>A) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Glu75= (c.225G>A) in the general population?

PRSS1 p.Glu75= (c.225G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

PRSS1 p.Glu75=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.225G>A · rs2485752484 · VCV1788588

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary chronic pancreatitis

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 -2.6	GERP -2.4
Overall
CADD	6.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
European (non-Finnish)	0.000339%	295,004

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: PRSS1
Protein: p.Glu75=
Coding: c.225G>A
dbSNP: rs2485752484
Type: single nucleotide variant
Location: chr7:142751798 (GRCh38)

Full PRSS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary chronic pancreatitis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant hereditary chronic pancreatitis (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood
Prevalence: 1-9 / 1 000 000 (France)

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/prss1-p-glu75 (accessed [today's date]).

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