Is PRSS1 p.Arg116Pro (c.347G>C) pathogenic?

PRSS1 p.Arg116Pro (c.347G>C) is classified Likely pathogenic in PRSS1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0969); Ultra-rare (popmax 0.032%, afr); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Arg116Pro (c.347G>C)?

PRSS1 p.Arg116Pro (c.347G>C) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Arg116Pro (c.347G>C) in the general population?

PRSS1 p.Arg116Pro (c.347G>C) is ultra-rare (popmax 0.032%, afr) (gnomAD).

What do computational predictors say about PRSS1 p.Arg116Pro (c.347G>C)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

PRSS1 p.Arg116Pro

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.347G>C · rs199769221 · VCV161986

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign ⚠ discordant with ClinVar
REVEL	0.36	indeterminate
SaProt	LLR -3.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.23	GERP -0.11
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	1.396	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 0.032% African / African-American · 21/65,694 alleles

Filtering AF 0.0214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.00368% 56/1,523,686 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.119%	840
African / African-Americangrpmax	0.032%	3,128
Ashkenazi Jewishnot grpmax-eligible	0.00715%	13,989
Remaining individualsnot grpmax-eligible	0.0067%	14,935
Admixed American	0.00367%	27,218
European (non-Finnish)	0.00215%	46,501
Finnishnot grpmax-eligible	0.00166%	60,152
South Asian	0.00113%	88,534

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg116Pro
Coding: c.347G>C
MANE Select: NM_002769
dbSNP: rs199769221
Type: single nucleotide variant
Location: chr7:142751920 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB
Residue 116: a UniProt-annotated variant site (in pctt); an α-helix; the peptidase s1 domain

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.Arg116Cys Pathogenic/Likely pathogenic ★★ same residue
PRSS1 p.Arg116His Uncertain significance ★★ ⚠ same residue
PRSS1 p.Arg116Ser Uncertain significance ★ ⚠ same residue
PRSS1 p.Arg116= Likely benign ★ same residue
PRSS1 p.Ala16Val 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-arg116pro (accessed [today's date]).

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