Is PRSS1 p.Pro17Arg (c.50C>G) pathogenic?

PRSS1 p.Pro17Arg (c.50C>G) is classified Uncertain significance in PRSS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-15). AlphaMissense: likely benign (0.2006); Very rare (popmax 8.48e-05%, nfe); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Pro17Arg (c.50C>G)?

PRSS1 p.Pro17Arg (c.50C>G) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Pro17Arg (c.50C>G) in the general population?

PRSS1 p.Pro17Arg (c.50C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PRSS1 p.Pro17Arg (c.50C>G)?

AlphaMissense predicts likely benign (score 0.2006) — an in-silico prediction, not a clinical call.

PRSS1 p.Pro17Arg

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.50C>G · rs776401461 · VCV1745334

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.2006	likely benign
REVEL	0.547	indeterminate
SaProt	LLR -9.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.86, phastCons 0.23
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,874 alleles

Overall 6.2e-05% 1/1,614,020 alleles · very rare exomes 1/1,461,656 · genomes 0/152,364 · joint denominator

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.Pro17Arg
Coding: c.50C>G
MANE Select: NM_002769
dbSNP: rs776401461
Type: single nucleotide variant
Location: chr7:142750564 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB

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)

Similar variants

PRSS1 p.Pro17His Uncertain significance ★★ ⚠ same residue
PRSS1 p.Pro17Leu Uncertain significance ★★ same residue
PRSS1 p.Pro17= Likely benign ★★ same residue
PRSS1 p.Ala16Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRSS1 p.Arg116Cys Pathogenic/Likely pathogenic ★★ same condition
PRSS1 p.Arg122Cys Pathogenic ★★ same condition
PRSS1 p.Arg122His Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRSS1 p.Asn29Ile Pathogenic ★★ ⚠ same condition

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-pro17arg (accessed [today's date]).

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