Is PRSS1 p.Ser114Phe (c.341C>T) pathogenic?

PRSS1 p.Ser114Phe (c.341C>T) is classified Uncertain significance in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). AlphaMissense: likely pathogenic (0.6002); Absent from gnomAD v4.1; Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Ser114Phe (c.341C>T)?

PRSS1 p.Ser114Phe (c.341C>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Ser114Phe (c.341C>T) in the general population?

PRSS1 p.Ser114Phe (c.341C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRSS1 p.Ser114Phe (c.341C>T)?

AlphaMissense predicts likely pathogenic (score 0.6002) — an in-silico prediction, not a clinical call.

PRSS1 p.Ser114Phe

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.341C>T · VCV3426319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6002 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.6002	likely pathogenic
REVEL	0.44	indeterminate
SaProt	LLR -13.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.84	GERP -0.46
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	18.59	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRSS1
Protein: p.Ser114Phe
Coding: c.341C>T
MANE Select: NM_002769
Type: single nucleotide variant
Location: chr7:142751914 (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.Ser114= Conflicting classifications of pathogenicity ★ same residue
PRSS1 p.Ser114Cys 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-ser114phe (accessed [today's date]).

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