Is PRSS1 p.Ala117= (c.351A>C) pathogenic?

PRSS1 p.Ala117= (c.351A>C) is classified Likely benign in PRSS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-15). Ultra-rare (popmax 0.0353%, afr); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Ala117= (c.351A>C)?

PRSS1 p.Ala117= (c.351A>C) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Ala117= (c.351A>C) in the general population?

PRSS1 p.Ala117= (c.351A>C) is ultra-rare (popmax 0.0353%, afr) (gnomAD).

PRSS1 p.Ala117=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.351A>C · rs606231346 · VCV161987

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0353%, afr)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.57	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.742	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0353% African / African-American · 24/67,952 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0207%

Overall 0.00375% 58/1,545,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0353%	2,831
Middle Eastern	0.0168%	5,942
Ashkenazi Jewishnot grpmax-eligible	0.00702%	14,246
Remaining individualsnot grpmax-eligible	0.00662%	15,110
European (non-Finnish)	0.00221%	45,220
Admixed American	0.00179%	55,968
South Asian	0.00112%	89,332

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.Ala117=
Coding: c.351A>C
MANE Select: NM_002769
dbSNP: rs606231346
Type: single nucleotide variant
Location: chr7:142751924 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB
Residue 117: a disulfide bond; 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.Ala117Gly Uncertain significance ★ same residue
PRSS1 p.Ala117Thr 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
PRSS1 c.200+1G>C Uncertain significance ★★ 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-ala117 (accessed [today's date]).

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