Is PRSS1 p.Glu85= (c.255G>A) pathogenic?

PRSS1 p.Glu85= (c.255G>A) is classified Benign in PRSS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-31). Ultra-rare (popmax 0.0435%, afr); Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Glu85= (c.255G>A)?

PRSS1 p.Glu85= (c.255G>A) is associated with hereditary chronic pancreatitis (ClinVar).

How common is PRSS1 p.Glu85= (c.255G>A) in the general population?

PRSS1 p.Glu85= (c.255G>A) is ultra-rare (popmax 0.0435%, afr) (gnomAD).

PRSS1 p.Glu85=

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.255G>A · rs376671702 · VCV1164543

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0435%, afr)

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -0.075, phastCons 0.052
Overall
CADD	3.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0435% African / African-American · 30/68,994 alleles

Filtering AF 0.0312% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00456% 73/1,599,406 alleles · ultra-rare exomes 26/1,461,886 · genomes 47/137,520 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0435%	2,300
East Asian	0.0224%	4,467
Middle Eastern	0.0166%	6,022
Finnishnot grpmax-eligible	0.0111%	8,983
Remaining individualsnot grpmax-eligible	0.00642%	15,571
Admixed American	0.00342%	29,275
South Asian	0.0022%	45,361
European (non-Finnish)	0.00145%	69,124

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.Glu85=
Coding: c.255G>A
MANE Select: NM_002769
dbSNP: rs376671702
Type: single nucleotide variant
Location: chr7:142751828 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB
Residue 85: a binding site; 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.Glu85Gln 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
PRSS1 c.201-7C>A 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-glu85 (accessed [today's date]).

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