Is PRSS1 p.Ser114= (c.342C>T) pathogenic?

PRSS1 p.Ser114= (c.342C>T) is classified Conflicting classifications of pathogenicity in PRSS1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-01). Very rare (popmax 0.00263%, nfe); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Ser114= (c.342C>T)?

PRSS1 p.Ser114= (c.342C>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Ser114= (c.342C>T) in the general population?

PRSS1 p.Ser114= (c.342C>T) is very rare (popmax 0.00263%, nfe) (gnomAD).

PRSS1 p.Ser114=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.342C>T · rs776924834 · VCV1128130

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -1.5	GERP 0.89
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00263% European (non-Finnish) · 31/1,180,022 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00192% 31/1,614,088 alleles · very rare exomes 31/1,461,890 · genomes 0/152,198 · 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.Ser114=
Coding: c.342C>T
MANE Select: NM_002769
dbSNP: rs776924834
Type: single nucleotide variant
Location: chr7:142751915 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB
Residue 114: a β-strand; 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.Ser114Cys Uncertain significance ★ ⚠ same residue
PRSS1 p.Ser114Phe Uncertain significance ★ ⚠ same residue
PRSS1 p.Ser114Pro Uncertain significance ★ ⚠ 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-ser114 (accessed [today's date]).

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