Is PRSS12 p.Phe65fs (c.192_193dup) pathogenic?

PRSS12 p.Phe65fs (c.192193dup) is classified Uncertain significance in PRSS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-13). Very rare (popmax 0.000271%, nfe).

How common is PRSS12 p.Phe65fs (c.192_193dup) in the general population?

PRSS12 p.Phe65fs (c.192_193dup) is very rare (popmax 0.000271%, nfe) (gnomAD).

PRSS12 p.Phe65fs

c.192_193dup · rs1243970842 · VCV1338330

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000271%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.18	GERP -0.44
Overall
CADD	19.23	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000271% European (non-Finnish) · 3/1,108,444 alleles

Filtering AF 7.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000203% 3/1,474,450 alleles · very rare

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: PRSS12
Protein: p.Phe65fs
Coding: c.192_193dup
MANE Select: NM_003619
dbSNP: rs1243970842
Type: Duplication
Location: chr4:118352527 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.42
Residue 65: the 'disordered' region

Full PRSS12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRSS12 p.Phe65= Uncertain significance ★ same residue
PRSS12 p.Gln710fs Uncertain significance ★★ same type
PRSS12 p.His473fs Conflicting classifications of pathogenicity ★ same type
PRSS12 p.Trp160fs Uncertain significance ★ same type

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/prss12-p-phe65fs (accessed [today's date]).

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