Is PRSS1 p.Ser124Phe (c.371C>T) pathogenic?

PRSS1 p.Ser124Phe (c.371C>T) is classified Uncertain significance in PRSS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-19). AlphaMissense: ambiguous (0.5513); Very rare (popmax 0.00223%, eas); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Ser124Phe (c.371C>T)?

PRSS1 p.Ser124Phe (c.371C>T) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Ser124Phe (c.371C>T) in the general population?

PRSS1 p.Ser124Phe (c.371C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PRSS1 p.Ser124Phe (c.371C>T)?

AlphaMissense predicts ambiguous (score 0.5513) — an in-silico prediction, not a clinical call.

PRSS1 p.Ser124Phe

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.371C>T · rs1484849588 · VCV1734271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
AlphaMissense	0.5513	ambiguous
REVEL	0.337	indeterminate
SaProt	LLR -11.58	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.69	GERP 1.9
Regional constraint	o/e 1.20	unconstrained · MANE · 3,532 bp · p 0.00039 · regional, not allelic
Overall
CADD	21.2	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 0.00223% East Asian · 1/44,876 alleles

Overall 6.2e-05% 1/1,614,022 alleles · very rare exomes 1/1,461,878 · genomes 0/152,144 · 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.Ser124Phe
Coding: c.371C>T
MANE Select: NM_002769
dbSNP: rs1484849588
Type: single nucleotide variant
Location: chr7:142751944 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB
Residue 124: 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.Ser124Thr Uncertain significance ★ ⚠ same residue
PRSS1 p.Ser124Tyr Uncertain significance ★ same residue
PRSS1 p.Ser124= 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-ser124phe (accessed [today's date]).

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