Is PRSS1 p.Asp162= (c.486T>C) pathogenic?

PRSS1 p.Asp162= (c.486T>C) is classified Benign/Likely benign in PRSS1 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 48.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary chronic pancreatitis.

What condition is associated with PRSS1 p.Asp162= (c.486T>C)?

PRSS1 p.Asp162= (c.486T>C) is associated with hereditary chronic pancreatitis (ClinVar).

PRSS1 p.Asp162=

Q: How common is PRSS1 p.Asp162= (c.486T>C) in the general population?

PRSS1 p.Asp162= (c.486T>C) is common (popmax 48.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.486T>C · rs6666 · VCV239391

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 48.8%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.7
Overall
CADD	0.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 48.8% African / African-American · 33,654/68,902 alleles

Filtering AF 48.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.2%

Overall 40.7% 648,977/1,595,478 alleles · common exomes 585,672/1,447,336 · genomes 63,305/148,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	48.8%	2
Finnishnot grpmax-eligible	42.5%	2
European (non-Finnish)	42%	2
Admixed American	41.6%	2
Ashkenazi Jewishnot grpmax-eligible	41%	2
Remaining individualsnot grpmax-eligible	38.9%	3
Amishnot grpmax-eligible	38.2%	3
Middle Eastern	35.2%	3
South Asian	26.3%	4
East Asian	21.5%	5

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.Asp162=
Coding: c.486T>C
MANE Select: NM_002769
dbSNP: rs6666
Type: single nucleotide variant
Location: chr7:142752462 (GRCh38)
Gene constraint: LOEUF 1.301 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.24 · 12 PDB
Residue 162: the peptidase s1 domain; a β-strand

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.Asp162Asn Uncertain significance ★★ ⚠ same residue
PRSS1 p.Asp162Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
PRSS1 p.Asp162His 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-asp162 (accessed [today's date]).

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