Is PIGA p.Pro372fs (c.1115del) pathogenic?

PIGA p.Pro372fs (c.1115del) is classified Pathogenic in PIGA (ClinVar, No assertion criteria, 1 submitter; last evaluated 1996-01-01). No gnomAD frequency available for this variant; Associated with paroxysmal nocturnal hemoglobinuria.

What condition is associated with PIGA p.Pro372fs (c.1115del)?

PIGA p.Pro372fs (c.1115del) is associated with paroxysmal nocturnal hemoglobinuria (ClinVar).

How common is PIGA p.Pro372fs (c.1115del) in the general population?

PIGA p.Pro372fs (c.1115del) is no gnomAD frequency available for this variant (gnomAD).

How is Paroxysmal nocturnal hemoglobinuria inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

PIGA p.Pro372fs

c.1115del · rs587776725 · VCV9960

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

paroxysmal nocturnal hemoglobinuria

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 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -4
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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: PIGA
Protein: p.Pro372fs
Coding: c.1115del
MANE Select: NM_002641
dbSNP: rs587776725
Type: Deletion
Location: chrX:15324738 (GRCh38)
Structure: AlphaFold pLDDT 86.22

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

Disease context

paroxysmal nocturnal hemoglobinuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Paroxysmal nocturnal hemoglobinuria (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

PIGA p.Pro372Leu Uncertain significance ★ ⚠ same residue
PIGA c.1188+2del Pathogenic same condition
PIGA p.Leu442fs Pathogenic same condition
PIGA p.Thr144fs Pathogenic same condition
PIGA p.Tyr98Ter Likely pathogenic ★ same condition
PIGA c.1188+1G>A Pathogenic same condition
PIGA p.Asp452delinsGluIleGluMetAspAspSerArgPheTyrHisTer Pathogenic same condition
PIGA p.Gln55Ter 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/piga-p-pro372fs (accessed [today's date]).

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