Is SPINK1 p.Cys61fs (c.182del) pathogenic?

SPINK1 p.Cys61fs (c.182del) is classified Conflicting classifications of pathogenicity in SPINK1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-05-10). Absent from gnomAD; Associated with hereditary chronic pancreatitis.

What condition is associated with SPINK1 p.Cys61fs (c.182del)?

SPINK1 p.Cys61fs (c.182del) is associated with hereditary chronic pancreatitis (ClinVar).

How common is SPINK1 p.Cys61fs (c.182del) in the general population?

SPINK1 p.Cys61fs (c.182del) is absent from gnomAD (gnomAD).

SPINK1 p.Cys61fs

Q: How is Autosomal dominant hereditary chronic pancreatitis inherited?

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

c.182del · rs2480198849 · VCV2414904

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary chronic pancreatitis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (3 of 4, 12 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.36	phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SPINK1
Protein: p.Cys61fs
Coding: c.182del
MANE Select: NM_001379610
dbSNP: rs2480198849
Type: Deletion
Location: chr5:147828034 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI 0.22 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.70 · 5 PDB
Residue 61: the kazal-like domain; an α-helix; a disulfide bond

Full SPINK1 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

SPINK1 p.Cys61Arg Uncertain significance ★ ⚠ same residue
SPINK1 p.Cys61= Likely benign ★ same residue
SPINK1 p.Ser10fs Pathogenic ★★ same condition
SPINK1 p.Asn56fs Likely pathogenic ★ same condition
SPINK1 p.Lys31_Tyr33del Conflicting classifications of pathogenicity ★ same condition
SPINK1 c.-191-129_56-932del Pathogenic same condition
SPINK1 c.194+2T>C Pathogenic/Likely pathogenic ★★ same condition
SPINK1 p.Glu35Ter 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/spink1-p-cys61fs (accessed [today's date]).

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