Is PRSS12 p.Pro341fs (c.1022del) pathogenic?

PRSS12 p.Pro341fs (c.1022del) is classified Likely pathogenic in PRSS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). Very rare (popmax 0.0011%, sas); Associated with intellectual disability, autosomal recessive 1.

What condition is associated with PRSS12 p.Pro341fs (c.1022del)?

PRSS12 p.Pro341fs (c.1022del) is associated with intellectual disability, autosomal recessive 1 (ClinVar).

How common is PRSS12 p.Pro341fs (c.1022del) in the general population?

PRSS12 p.Pro341fs (c.1022del) is very rare (popmax 0.0011%, sas) (gnomAD).

PRSS12 p.Pro341fs

c.1022del · VCV4849491

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

intellectual disability, autosomal recessive 1

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 5 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.7	GERP -3.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,088 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,154 alleles · very rare exomes 3/1,461,828 · genomes 0/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,088
European (non-Finnish)	0.000169%	590,009

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.Pro341fs
Coding: c.1022del
MANE Select: NM_003619
Type: Deletion
Location: chr4:118318506 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.42
Residue 341: the srcr 2 domain

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

Disease context

intellectual disability, autosomal recessive 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRSS12 p.Trp148fs Likely pathogenic ★ same condition
PRSS12 p.Met830fs Conflicting classifications of pathogenicity ★ same condition
PRSS12 c.2320+6G>C Uncertain significance ★★ same condition
PRSS12 c.821-1G>A Uncertain significance ★★ same condition
PRSS12 c.*1615C>T Uncertain significance ★★ same condition
PRSS12 c.*221A>T Uncertain significance ★★ same condition
PRSS12 p.Ala547Asp Uncertain significance ★★ ⚠ same condition
PRSS12 p.Ala79Pro 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/prss12-p-pro341fs (accessed [today's date]).

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