Is PRSS1 p.Arg95Pro (c.284G>C) pathogenic?

PRSS1 p.Arg95Pro (c.284G>C) is classified Uncertain significance in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: ambiguous (0.3495); Very rare (popmax 0.000169%, nfe); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Arg95Pro (c.284G>C)?

PRSS1 p.Arg95Pro (c.284G>C) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Arg95Pro (c.284G>C) in the general population?

PRSS1 p.Arg95Pro (c.284G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about PRSS1 p.Arg95Pro (c.284G>C)?

AlphaMissense predicts ambiguous (score 0.3495) — an in-silico prediction, not a clinical call.

PRSS1 p.Arg95Pro

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.284G>C · rs375820192 · VCV1796818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3495 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.3495	ambiguous
REVEL	0.552	indeterminate
SaProt	LLR -10.14	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.86	GERP -1.2
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	17.53	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,002 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,884 alleles · very rare

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.Arg95Pro
Coding: c.284G>C
dbSNP: rs375820192
Type: single nucleotide variant
Location: chr7:142751857 (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-arg95pro (accessed [today's date]).

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