Is PRSS1 p.Pro36Arg (c.107C>G) pathogenic?

PRSS1 p.Pro36Arg (c.107C>G) is classified Uncertain significance in PRSS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-20). AlphaMissense: ambiguous (0.3803); Ultra-rare (popmax 0.0869%, eas); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Pro36Arg (c.107C>G)?

PRSS1 p.Pro36Arg (c.107C>G) is associated with hereditary chronic pancreatitis, trypsinogen deficiency (ClinVar).

How common is PRSS1 p.Pro36Arg (c.107C>G) in the general population?

PRSS1 p.Pro36Arg (c.107C>G) is ultra-rare (popmax 0.0869%, eas) (gnomAD).

What do computational predictors say about PRSS1 p.Pro36Arg (c.107C>G)?

AlphaMissense predicts ambiguous (score 0.3803) — an in-silico prediction, not a clinical call.

PRSS1 p.Pro36Arg

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.107C>G · rs769459903 · VCV459181

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3803 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.3803	ambiguous
REVEL	0.971	strongly pathogenic-leaning
SaProt	LLR -10.58	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	26.5	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 0.0869% East Asian · 39/44,890 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00248% 40/1,614,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0869%	1,151
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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.Pro36Arg
Coding: c.107C>G
dbSNP: rs769459903
Type: single nucleotide variant
Location: chr7:142750621 (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

Also linked: trypsinogen deficiency

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-pro36arg (accessed [today's date]).

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