Is PRSS56 p.Arg74fs (c.219del) pathogenic?

PRSS56 p.Arg74fs (c.219del) is classified Pathogenic/Likely pathogenic in PRSS56 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-24). Absent from gnomAD v4.1; Associated with isolated microphthalmia 6.

What condition is associated with PRSS56 p.Arg74fs (c.219del)?

PRSS56 p.Arg74fs (c.219del) is associated with isolated microphthalmia 6 (ClinVar).

How common is PRSS56 p.Arg74fs (c.219del) in the general population?

PRSS56 p.Arg74fs (c.219del) is absent from gnomAD v4.1 (gnomAD).

PRSS56 p.Arg74fs

c.219del · rs1218404300 · VCV1333280

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,536,018)

Conditions

isolated microphthalmia 6

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 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.53	GERP -3.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,536,018). 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: PRSS56
Protein: p.Arg74fs
Coding: c.219del
MANE Select: NM_001195129
dbSNP: rs1218404300
Type: Deletion
Location: chr2:232521826 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.35
Residue 74: the 'disordered' region

Full PRSS56 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

isolated microphthalmia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRSS56 p.Gln356fs Pathogenic ★★ same condition
PRSS56 p.Val525fs Pathogenic/Likely pathogenic ★★ same condition
PRSS56 c.205+18del Benign ★★ same condition
PRSS56 p.Gln217fs Pathogenic ★ same condition
PRSS56 p.Gln32fs Likely pathogenic ★ same condition
PRSS56 p.Arg74Gly Uncertain significance ★ ⚠ same residue
PRSS56 p.Glu477_Gln481del Uncertain significance ★ same condition
PRSS56 p.Pro28del 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/prss56-p-arg74fs (accessed [today's date]).

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